The Experts below are selected from a list of 32589 Experts worldwide ranked by ideXlab platform
Jürgen Schweizer - One of the best experts on this subject based on the ideXlab platform.
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new consensus nomenclature for mammalian Keratins
Journal of Cell Biology, 2006Co-Authors: Jürgen Schweizer, Birgitte E Lane, Lutz Langbein, Thomas M. Magin, Bishr M Omary, David A D Parry, Pierre A Coulombe, Paul Edward Bowden, Lois J Maltais, Michael A. RogersAbstract:Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the Keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel Keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for Keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human Keratins, it offers the flexibility needed to incorporate additional Keratins from other mammalian species.
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characterization of new members of the human type ii Keratin gene family and a general evaluation of the Keratin gene domain on chromosome 12q13 13
Journal of Investigative Dermatology, 2005Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Lutz Edler, Iris Beckmann, Jürgen SchweizerAbstract:The recent completion of a reference sequence of the human genome now allows a complete characterization of the type II Keratin gene domain on chromosome 12q13.13. This, domain, approximately 780 kb in size, is present on nine bacterial artificial chromosome clones sequenced by the Human Genome Sequencing Project. The type II Keratin domain contains 27 Keratin genes and eight pseudogenes. Twenty-three of these genes and four pseudogenes have been previously reported. This study describes, in addition to the genomic sequencing of the K2p gene and the bioinformatic identification of four Keratin pseudogenes, the characterization of cDNA corresponding to three previously undescribed Keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously described Keratin genes hHb2, hHb4, and K3. Northern analysis of the new Keratins K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific epithelial subtypes shows singular expression of these Keratins in skin, hair follicles and, for K5b and Kb20, in tongue, respectively. In addition, the obvious discrepancies between the current reference sequence of the human genome and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are probably polymorphic variants of K6a and K6h, respectively. All 26 human type II Keratins found on this domain as well as K18, dtype 1 Keratin, are identified at the genomic and transcriptional level. This appears to be the total complement of functional type II Keratins in humans.
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the human type i Keratin gene family characterization of new hair follicle specific members and evaluation of the chromosome 17q21 2 gene domain
Differentiation, 2004Co-Authors: Michael A. Rogers, Raphael Bleiler, Hermelita Winter, Lutz Langbein, Jürgen SchweizerAbstract:Abstract In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence found in the EBI/Genebank database shows the presence of 27 type I Keratin genes and five Keratin pseudogenes present on 8 contiguous Bacterial Artificial Chromosome (BAC) sequences. This constitutes the 970 kb type I Keratin gene domain. Inserted into this domain is a 350 kb region harboring 32 previously characterized Keratin-associated protein genes. Of the 27 Keratin genes found in this region, six have not been characterized in detail. This study reports the isolation of cDNA sequences for these Keratin genes, termed K25irs1-K25irs4, Ka35, and Ka36, as well as cDNA sequences for the previously reported hair Keratins hHa3-I, hHa7, and hHa8. RT-PCR analysis of 14 epithelial tissues using primers for the six novel Keratins, as well as for Keratins 23 and 24, shows that the six novel Keratins appear to be hair follicle associated. Previous expression data, coupled with evolutionary analysis studies point to K25irs1–K25irs4 probably being inner root sheath specific Keratins. Ka35 and Ka36 are, based on their exon–intron structure and expression characteristics, hair Keratins. In contrast, K23 and K24 appear to be epithelial Keratins associated with simple/glandular or stratified, non-cornified epithelia, respectively. A literature analysis coupled with the data presented here confirms that all of the 27 Keratin genes found on this domain have been characterized at the transcriptional level. Together with K18, a type I Keratin gene found on the type II Keratin domain, this seems to be the entire complement of functional type I Keratins in humans.
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characterization of a 300 kbp region of human dna containing the type ii hair Keratin gene domain
Journal of Investigative Dermatology, 2000Co-Authors: Michael A. Rogers, Hermelita Winter, Jürgen Schweizer, Christian Wolf, Lutz LangbeinAbstract:Screening of an arrayed human genomic P1 artificial chromosome DNA library by means of the polymerase chain reaction with a specific primer pair from the human type II hair Keratin hHb5 yielded two P1 artificial chromosome clones covering ≈300 kb of genomic DNA. The contig contained six type II hair Keratin genes, hHb1–hHb6, and four Keratin pseudogenes ψhHbA–ψhHbD. This hair Keratin gene domain was flanked by type II epithelial Keratins K6b/K6hf and K7, respectively. The Keratin genes/pseudogene are 5–14 kbp in size with intergenic distances of 5–19 kbp of DNA and do not exhibit a single direction of transcription. With one exception, type II hair Keratin genes are organized into nine exons and eight introns, with strictly conserved exon–intron boundaries. The functional hair Keratin genes are grouped into two distinct subclusters near the extremities of the hair Keratin gene domain. One subcluster encodes the highly related hair Keratins hHb1, hHb3, and hHb6; The second cluster encodes the structurally less related hair Keratins hHb2, hHb4, and hHb5. Reverse transcription–polymerase chain reaction shows that all hair Keratin genes are expressed in the hair follicle. Pseudogene ψhHbD is also transcriptionally expressed, albeit with alterations in splicing and frameshift mutations, leading to premature stop codons in the splice forms analyzed. Evolutionary tree analysis revealed a divergence of the type II hair Keratin genes from the epithelial Keratins, followed by their segregation into the members of the two subclusters over time. We assume that the ≈200 kbp DNA domain contains the entire complement of human type II hair Keratin genes.
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sequence data and chromosomal localization of human type i and type ii hair Keratin genes
Experimental Cell Research, 1995Co-Authors: Michael A. Rogers, Hermelita Winter, Bernhard P Korge, Thomas Krieg, Roswitha Nischt, Thomas M Fink, Peter Lichter, Jürgen SchweizerAbstract:Abstract A cDNA library constructed with poly(A) + RNA from human scalp was screened with selected fragments of both murine type I and type II hair Keratin cDNAs. Two Keratin clones, one type I, phKI-2, and one type II, phKII-1, were isolated and sequenced. In Northern blots, cDNA probes containing the 3′-noncoding sequences of the clones specifically hybridized to scalp mRNA species. Based on sequence homology comparisons with the four known murine type I hair Keratins mHa1-4, the phKI-2 encoded Keratin could be identified as human hair Keratin hHa2. Similarly, sequence comparison with the four type II sheep wool Keratins K2.9-12 revealed an orthologous relationship between the largest member of the type II wool Keratin subfamily, K2.9 (i.e., sHb1) and the phKII-1 encoded human hair Keratin (hHb1). The specific 3′-noncoding sequences of hHa2 and hHb1 were also used to isolate genomic fragments for both Keratins from human genomic libraries which were than used for fluorescence in situ hybridization to human rectaphase chromosomes. The hHa2 gene could be mapped to the long arm of chromosome 17, whereas the hHb1 gene was found on the long arm of chromosome 12. DAPI banding of the chromosomes allowed sublocalization of the hHa2 gene to 17q12-q21 and the hHb1 gene to 12q13, i.e., gene loci that have also been previously determined for human type I and type II epithelial Keratins.
Michael A. Rogers - One of the best experts on this subject based on the ideXlab platform.
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new consensus nomenclature for mammalian Keratins
Journal of Cell Biology, 2006Co-Authors: Jürgen Schweizer, Birgitte E Lane, Lutz Langbein, Thomas M. Magin, Bishr M Omary, David A D Parry, Pierre A Coulombe, Paul Edward Bowden, Lois J Maltais, Michael A. RogersAbstract:Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the Keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel Keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for Keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human Keratins, it offers the flexibility needed to incorporate additional Keratins from other mammalian species.
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characterization of new members of the human type ii Keratin gene family and a general evaluation of the Keratin gene domain on chromosome 12q13 13
Journal of Investigative Dermatology, 2005Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Lutz Edler, Iris Beckmann, Jürgen SchweizerAbstract:The recent completion of a reference sequence of the human genome now allows a complete characterization of the type II Keratin gene domain on chromosome 12q13.13. This, domain, approximately 780 kb in size, is present on nine bacterial artificial chromosome clones sequenced by the Human Genome Sequencing Project. The type II Keratin domain contains 27 Keratin genes and eight pseudogenes. Twenty-three of these genes and four pseudogenes have been previously reported. This study describes, in addition to the genomic sequencing of the K2p gene and the bioinformatic identification of four Keratin pseudogenes, the characterization of cDNA corresponding to three previously undescribed Keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously described Keratin genes hHb2, hHb4, and K3. Northern analysis of the new Keratins K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific epithelial subtypes shows singular expression of these Keratins in skin, hair follicles and, for K5b and Kb20, in tongue, respectively. In addition, the obvious discrepancies between the current reference sequence of the human genome and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are probably polymorphic variants of K6a and K6h, respectively. All 26 human type II Keratins found on this domain as well as K18, dtype 1 Keratin, are identified at the genomic and transcriptional level. This appears to be the total complement of functional type II Keratins in humans.
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the human type i Keratin gene family characterization of new hair follicle specific members and evaluation of the chromosome 17q21 2 gene domain
Differentiation, 2004Co-Authors: Michael A. Rogers, Raphael Bleiler, Hermelita Winter, Lutz Langbein, Jürgen SchweizerAbstract:Abstract In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence found in the EBI/Genebank database shows the presence of 27 type I Keratin genes and five Keratin pseudogenes present on 8 contiguous Bacterial Artificial Chromosome (BAC) sequences. This constitutes the 970 kb type I Keratin gene domain. Inserted into this domain is a 350 kb region harboring 32 previously characterized Keratin-associated protein genes. Of the 27 Keratin genes found in this region, six have not been characterized in detail. This study reports the isolation of cDNA sequences for these Keratin genes, termed K25irs1-K25irs4, Ka35, and Ka36, as well as cDNA sequences for the previously reported hair Keratins hHa3-I, hHa7, and hHa8. RT-PCR analysis of 14 epithelial tissues using primers for the six novel Keratins, as well as for Keratins 23 and 24, shows that the six novel Keratins appear to be hair follicle associated. Previous expression data, coupled with evolutionary analysis studies point to K25irs1–K25irs4 probably being inner root sheath specific Keratins. Ka35 and Ka36 are, based on their exon–intron structure and expression characteristics, hair Keratins. In contrast, K23 and K24 appear to be epithelial Keratins associated with simple/glandular or stratified, non-cornified epithelia, respectively. A literature analysis coupled with the data presented here confirms that all of the 27 Keratin genes found on this domain have been characterized at the transcriptional level. Together with K18, a type I Keratin gene found on the type II Keratin domain, this seems to be the entire complement of functional type I Keratins in humans.
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the catalog of human hair Keratins ii expression of the six type ii members in the hair follicle and the combined catalog of human type i and ii Keratins
Journal of Biological Chemistry, 2001Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, J SchweizerAbstract:Abstract The human type II hair Keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual hair Keratins were used to establish the two-dimensional catalog of human type II hair Keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of hair Keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen hair follicles showed that hHb5 and hHb2 defined early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II hair Keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This hair Keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I hair Keratin expression profiles suggested specific, but more likely, random Keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I hair Keratin catalog with the type II hair Keratin catalog and integrating both into the existing catalog of human epithelial Keratins, we present a two-dimensional compilation of the presently known human Keratins.
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characterization of a 300 kbp region of human dna containing the type ii hair Keratin gene domain
Journal of Investigative Dermatology, 2000Co-Authors: Michael A. Rogers, Hermelita Winter, Jürgen Schweizer, Christian Wolf, Lutz LangbeinAbstract:Screening of an arrayed human genomic P1 artificial chromosome DNA library by means of the polymerase chain reaction with a specific primer pair from the human type II hair Keratin hHb5 yielded two P1 artificial chromosome clones covering ≈300 kb of genomic DNA. The contig contained six type II hair Keratin genes, hHb1–hHb6, and four Keratin pseudogenes ψhHbA–ψhHbD. This hair Keratin gene domain was flanked by type II epithelial Keratins K6b/K6hf and K7, respectively. The Keratin genes/pseudogene are 5–14 kbp in size with intergenic distances of 5–19 kbp of DNA and do not exhibit a single direction of transcription. With one exception, type II hair Keratin genes are organized into nine exons and eight introns, with strictly conserved exon–intron boundaries. The functional hair Keratin genes are grouped into two distinct subclusters near the extremities of the hair Keratin gene domain. One subcluster encodes the highly related hair Keratins hHb1, hHb3, and hHb6; The second cluster encodes the structurally less related hair Keratins hHb2, hHb4, and hHb5. Reverse transcription–polymerase chain reaction shows that all hair Keratin genes are expressed in the hair follicle. Pseudogene ψhHbD is also transcriptionally expressed, albeit with alterations in splicing and frameshift mutations, leading to premature stop codons in the splice forms analyzed. Evolutionary tree analysis revealed a divergence of the type II hair Keratin genes from the epithelial Keratins, followed by their segregation into the members of the two subclusters over time. We assume that the ≈200 kbp DNA domain contains the entire complement of human type II hair Keratin genes.
Hermelita Winter - One of the best experts on this subject based on the ideXlab platform.
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characterization of new members of the human type ii Keratin gene family and a general evaluation of the Keratin gene domain on chromosome 12q13 13
Journal of Investigative Dermatology, 2005Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Lutz Edler, Iris Beckmann, Jürgen SchweizerAbstract:The recent completion of a reference sequence of the human genome now allows a complete characterization of the type II Keratin gene domain on chromosome 12q13.13. This, domain, approximately 780 kb in size, is present on nine bacterial artificial chromosome clones sequenced by the Human Genome Sequencing Project. The type II Keratin domain contains 27 Keratin genes and eight pseudogenes. Twenty-three of these genes and four pseudogenes have been previously reported. This study describes, in addition to the genomic sequencing of the K2p gene and the bioinformatic identification of four Keratin pseudogenes, the characterization of cDNA corresponding to three previously undescribed Keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously described Keratin genes hHb2, hHb4, and K3. Northern analysis of the new Keratins K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific epithelial subtypes shows singular expression of these Keratins in skin, hair follicles and, for K5b and Kb20, in tongue, respectively. In addition, the obvious discrepancies between the current reference sequence of the human genome and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are probably polymorphic variants of K6a and K6h, respectively. All 26 human type II Keratins found on this domain as well as K18, dtype 1 Keratin, are identified at the genomic and transcriptional level. This appears to be the total complement of functional type II Keratins in humans.
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the human type i Keratin gene family characterization of new hair follicle specific members and evaluation of the chromosome 17q21 2 gene domain
Differentiation, 2004Co-Authors: Michael A. Rogers, Raphael Bleiler, Hermelita Winter, Lutz Langbein, Jürgen SchweizerAbstract:Abstract In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence found in the EBI/Genebank database shows the presence of 27 type I Keratin genes and five Keratin pseudogenes present on 8 contiguous Bacterial Artificial Chromosome (BAC) sequences. This constitutes the 970 kb type I Keratin gene domain. Inserted into this domain is a 350 kb region harboring 32 previously characterized Keratin-associated protein genes. Of the 27 Keratin genes found in this region, six have not been characterized in detail. This study reports the isolation of cDNA sequences for these Keratin genes, termed K25irs1-K25irs4, Ka35, and Ka36, as well as cDNA sequences for the previously reported hair Keratins hHa3-I, hHa7, and hHa8. RT-PCR analysis of 14 epithelial tissues using primers for the six novel Keratins, as well as for Keratins 23 and 24, shows that the six novel Keratins appear to be hair follicle associated. Previous expression data, coupled with evolutionary analysis studies point to K25irs1–K25irs4 probably being inner root sheath specific Keratins. Ka35 and Ka36 are, based on their exon–intron structure and expression characteristics, hair Keratins. In contrast, K23 and K24 appear to be epithelial Keratins associated with simple/glandular or stratified, non-cornified epithelia, respectively. A literature analysis coupled with the data presented here confirms that all of the 27 Keratin genes found on this domain have been characterized at the transcriptional level. Together with K18, a type I Keratin gene found on the type II Keratin domain, this seems to be the entire complement of functional type I Keratins in humans.
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the catalog of human hair Keratins ii expression of the six type ii members in the hair follicle and the combined catalog of human type i and ii Keratins
Journal of Biological Chemistry, 2001Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, J SchweizerAbstract:Abstract The human type II hair Keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual hair Keratins were used to establish the two-dimensional catalog of human type II hair Keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of hair Keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen hair follicles showed that hHb5 and hHb2 defined early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II hair Keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This hair Keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I hair Keratin expression profiles suggested specific, but more likely, random Keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I hair Keratin catalog with the type II hair Keratin catalog and integrating both into the existing catalog of human epithelial Keratins, we present a two-dimensional compilation of the presently known human Keratins.
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characterization of a 300 kbp region of human dna containing the type ii hair Keratin gene domain
Journal of Investigative Dermatology, 2000Co-Authors: Michael A. Rogers, Hermelita Winter, Jürgen Schweizer, Christian Wolf, Lutz LangbeinAbstract:Screening of an arrayed human genomic P1 artificial chromosome DNA library by means of the polymerase chain reaction with a specific primer pair from the human type II hair Keratin hHb5 yielded two P1 artificial chromosome clones covering ≈300 kb of genomic DNA. The contig contained six type II hair Keratin genes, hHb1–hHb6, and four Keratin pseudogenes ψhHbA–ψhHbD. This hair Keratin gene domain was flanked by type II epithelial Keratins K6b/K6hf and K7, respectively. The Keratin genes/pseudogene are 5–14 kbp in size with intergenic distances of 5–19 kbp of DNA and do not exhibit a single direction of transcription. With one exception, type II hair Keratin genes are organized into nine exons and eight introns, with strictly conserved exon–intron boundaries. The functional hair Keratin genes are grouped into two distinct subclusters near the extremities of the hair Keratin gene domain. One subcluster encodes the highly related hair Keratins hHb1, hHb3, and hHb6; The second cluster encodes the structurally less related hair Keratins hHb2, hHb4, and hHb5. Reverse transcription–polymerase chain reaction shows that all hair Keratin genes are expressed in the hair follicle. Pseudogene ψhHbD is also transcriptionally expressed, albeit with alterations in splicing and frameshift mutations, leading to premature stop codons in the splice forms analyzed. Evolutionary tree analysis revealed a divergence of the type II hair Keratin genes from the epithelial Keratins, followed by their segregation into the members of the two subclusters over time. We assume that the ≈200 kbp DNA domain contains the entire complement of human type II hair Keratin genes.
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sequence data and chromosomal localization of human type i and type ii hair Keratin genes
Experimental Cell Research, 1995Co-Authors: Michael A. Rogers, Hermelita Winter, Bernhard P Korge, Thomas Krieg, Roswitha Nischt, Thomas M Fink, Peter Lichter, Jürgen SchweizerAbstract:Abstract A cDNA library constructed with poly(A) + RNA from human scalp was screened with selected fragments of both murine type I and type II hair Keratin cDNAs. Two Keratin clones, one type I, phKI-2, and one type II, phKII-1, were isolated and sequenced. In Northern blots, cDNA probes containing the 3′-noncoding sequences of the clones specifically hybridized to scalp mRNA species. Based on sequence homology comparisons with the four known murine type I hair Keratins mHa1-4, the phKI-2 encoded Keratin could be identified as human hair Keratin hHa2. Similarly, sequence comparison with the four type II sheep wool Keratins K2.9-12 revealed an orthologous relationship between the largest member of the type II wool Keratin subfamily, K2.9 (i.e., sHb1) and the phKII-1 encoded human hair Keratin (hHb1). The specific 3′-noncoding sequences of hHa2 and hHb1 were also used to isolate genomic fragments for both Keratins from human genomic libraries which were than used for fluorescence in situ hybridization to human rectaphase chromosomes. The hHa2 gene could be mapped to the long arm of chromosome 17, whereas the hHb1 gene was found on the long arm of chromosome 12. DAPI banding of the chromosomes allowed sublocalization of the hHa2 gene to 17q12-q21 and the hHb1 gene to 12q13, i.e., gene loci that have also been previously determined for human type I and type II epithelial Keratins.
Lutz Langbein - One of the best experts on this subject based on the ideXlab platform.
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the Keratins of the human beard hair medulla the riddle in the middle
Journal of Investigative Dermatology, 2010Co-Authors: Lutz Langbein, Silke Praetzelwunder, Hiroshi Yoshida, David A D Parry, Juergen SchweizerAbstract:We have investigated the expression of 52 of the 54 Keratins in beard hair medulla. We found that not only 12 hair Keratins but, unexpectedly, also 12 epithelial Keratins are potentially expressed in medulla cells. The latter comprise Keratins also present in outer- and inner-root sheaths and in the companion layer. Keratins K5, K14, K17, K25, K27, K28, and K75 define a "pre-medulla," composed of cells apposed to the upper dermal papilla. Besides K6, K16, K7, K19, and K80, all pre-medullary epithelial Keratins continue to be expressed in the medulla proper, along with the 12 hair Keratins. Besides this unique feature of cellular Keratin co-expression, the Keratin pattern itself is highly variable in individual medulla cells. Remarkably, both epithelial and hair Keratins behave highly promiscuously with regard to heterodimer- and IF formation, which also includes Keratin chain interactions in IF bundles. We also identified cortex cells within the medullary column. These exhibit all the properties of genuine cortex cells, including a particular type of Keratin heterogeneity of their compact IF bundles. In both Keratin expression profile and Keratin number, medulla cells are distinct from all other cells of the hair follicle or from any other epithelium.
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new consensus nomenclature for mammalian Keratins
Journal of Cell Biology, 2006Co-Authors: Jürgen Schweizer, Birgitte E Lane, Lutz Langbein, Thomas M. Magin, Bishr M Omary, David A D Parry, Pierre A Coulombe, Paul Edward Bowden, Lois J Maltais, Michael A. RogersAbstract:Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the Keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel Keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for Keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human Keratins, it offers the flexibility needed to incorporate additional Keratins from other mammalian species.
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characterization of new members of the human type ii Keratin gene family and a general evaluation of the Keratin gene domain on chromosome 12q13 13
Journal of Investigative Dermatology, 2005Co-Authors: Michael A. Rogers, Hermelita Winter, Lutz Langbein, Lutz Edler, Iris Beckmann, Jürgen SchweizerAbstract:The recent completion of a reference sequence of the human genome now allows a complete characterization of the type II Keratin gene domain on chromosome 12q13.13. This, domain, approximately 780 kb in size, is present on nine bacterial artificial chromosome clones sequenced by the Human Genome Sequencing Project. The type II Keratin domain contains 27 Keratin genes and eight pseudogenes. Twenty-three of these genes and four pseudogenes have been previously reported. This study describes, in addition to the genomic sequencing of the K2p gene and the bioinformatic identification of four Keratin pseudogenes, the characterization of cDNA corresponding to three previously undescribed Keratin genes K1b, K6l, and Kb20, as well as cDNA sequences for the previously described Keratin genes hHb2, hHb4, and K3. Northern analysis of the new Keratins K1b, K6l, K5b, and Kb20 using mRNA of major organs as well as of specific epithelial subtypes shows singular expression of these Keratins in skin, hair follicles and, for K5b and Kb20, in tongue, respectively. In addition, the obvious discrepancies between the current reference sequence of the human genome and the previously described gene/cDNA sequences for K6c, K6d, K6e, K6f, K6h are investigated, leading to the conclusion that K6c, K6d as well as K6e, K6f are probably polymorphic variants of K6a and K6h, respectively. All 26 human type II Keratins found on this domain as well as K18, dtype 1 Keratin, are identified at the genomic and transcriptional level. This appears to be the total complement of functional type II Keratins in humans.
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the human type i Keratin gene family characterization of new hair follicle specific members and evaluation of the chromosome 17q21 2 gene domain
Differentiation, 2004Co-Authors: Michael A. Rogers, Raphael Bleiler, Hermelita Winter, Lutz Langbein, Jürgen SchweizerAbstract:Abstract In general concurrence with recent studies, bioinformatic analysis of the chromosome 17q21.2 DNA sequence found in the EBI/Genebank database shows the presence of 27 type I Keratin genes and five Keratin pseudogenes present on 8 contiguous Bacterial Artificial Chromosome (BAC) sequences. This constitutes the 970 kb type I Keratin gene domain. Inserted into this domain is a 350 kb region harboring 32 previously characterized Keratin-associated protein genes. Of the 27 Keratin genes found in this region, six have not been characterized in detail. This study reports the isolation of cDNA sequences for these Keratin genes, termed K25irs1-K25irs4, Ka35, and Ka36, as well as cDNA sequences for the previously reported hair Keratins hHa3-I, hHa7, and hHa8. RT-PCR analysis of 14 epithelial tissues using primers for the six novel Keratins, as well as for Keratins 23 and 24, shows that the six novel Keratins appear to be hair follicle associated. Previous expression data, coupled with evolutionary analysis studies point to K25irs1–K25irs4 probably being inner root sheath specific Keratins. Ka35 and Ka36 are, based on their exon–intron structure and expression characteristics, hair Keratins. In contrast, K23 and K24 appear to be epithelial Keratins associated with simple/glandular or stratified, non-cornified epithelia, respectively. A literature analysis coupled with the data presented here confirms that all of the 27 Keratin genes found on this domain have been characterized at the transcriptional level. Together with K18, a type I Keratin gene found on the type II Keratin domain, this seems to be the entire complement of functional type I Keratins in humans.
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the catalog of human hair Keratins ii expression of the six type ii members in the hair follicle and the combined catalog of human type i and ii Keratins
Journal of Biological Chemistry, 2001Co-Authors: Lutz Langbein, Silke Praetzel, Hermelita Winter, Michael A. Rogers, J SchweizerAbstract:Abstract The human type II hair Keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual hair Keratins were used to establish the two-dimensional catalog of human type II hair Keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of hair Keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen hair follicles showed that hHb5 and hHb2 defined early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II hair Keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This hair Keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I hair Keratin expression profiles suggested specific, but more likely, random Keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I hair Keratin catalog with the type II hair Keratin catalog and integrating both into the existing catalog of human epithelial Keratins, we present a two-dimensional compilation of the presently known human Keratins.
Bishr M Omary - One of the best experts on this subject based on the ideXlab platform.
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Brief Report Keratins Turn Over by Ubiquitination in a Phosphorylation-modulated Fashion
2013Co-Authors: Bishr M OmaryAbstract:Abstract. Keratin polypeptides 8 and 18 (K8/18) are intermediate filament (IF) proteins that are expressed in glandular epithelia. Although the mechanism of Keratin turnover is poorly understood, caspase-mediated degradation of type I Keratins occurs during apoptosis and the proteasome pathway has been indirectly implicated in Keratin turnover based on colocalization of Keratinubiquitin antibody staining. Here we show that K8 and K18 are ubiquitinated based on cotransfection of Histagged ubiquitin and human K8 and/or K18 cDNAs, followed by purification of ubiquitinated proteins and immunoblotting with Keratin antibodies. Transfection of K8 or K18 alone yields higher levels of Keratin ubiquitination as compared with cotransfection of K8/18, likely due to stabilization of the Keratin heteropolymer. Most of the ubiquitinated species partition with the noncytosolic Keratin fraction. Proteasome inhibition stabilizes K8 and K18 turnover, and is associated with accumulation of phosphorylated Keratins, which indicates that although Keratins are stable they still turnover. Analysis of K8 and K18 ubiquitination and degradation showed that K8 phosphorylation contributes to its stabilization. Our results provide direct evidence for K8 and K18 ubiquitination, in a phosphorylation modulated fashion, as a mechanism for regulating their turnover and suggest that other IF proteins could undergo similar regulation. These and other data offer a model that links Keratin ubiquitination and hyperphosphorylation that, in turn, are associated with Mallory body deposits in a variety of liver diseases. Key words: ubiquitination • Keratins • phosphorylation • intermediate filaments • Mallory bodie
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unique amino acid signatures that are evolutionarily conserved distinguish simple type epidermal and hair Keratins
Journal of Cell Science, 2011Co-Authors: Pavel Strnad, David A D Parry, Valentyn Usachov, Cedric Debes, Frauke Grater, Bishr M OmaryAbstract:Keratins (Ks) consist of central α-helical rod domains that are flanked by non-α-helical head and tail domains. The cellular abundance of Keratins, coupled with their selective cell expression patterns, suggests that they diversified to fulfill tissue-specific functions although the primary structure differences between them have not been comprehensively compared. We analyzed Keratin sequences from many species: K1, K2, K5, K9, K10, K14 were studied as representatives of epidermal Keratins, and compared with K7, K8, K18, K19, K20 and K31, K35, K81, K85, K86, which represent simple-type (single-layered or glandular) epithelial and hair Keratins, respectively. We show that Keratin domains have striking differences in their amino acids. There are many cysteines in hair Keratins but only a small number in epidermal Keratins and rare or none in simple-type Keratins. The heads and/or tails of epidermal Keratins are glycine and phenylalanine rich but alanine poor, whereas parallel domains of hair Keratins are abundant in prolines, and those of simple-type epithelial Keratins are enriched in acidic and/or basic residues. The observed differences between simple-type, epidermal and hair Keratins are highly conserved throughout evolution. Cysteines and histidines, which are infrequent Keratin amino acids, are involved in de novo mutations that are markedly overrepresented in Keratins. Hence, Keratins have evolutionarily conserved and domain-selectively enriched amino acids including glycine and phenylalanine (epidermal), cysteine and proline (hair), and basic and acidic (simple-type epithelial), which reflect unique functions related to structural flexibility, rigidity and solubility, respectively. Our findings also support the importance of human Keratin ‘mutation hotspot’ residues and their wild-type counterparts.
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Keratins modulate the shape and function of hepatocyte mitochondria a mechanism for protection from apoptosis
Journal of Cell Science, 2009Co-Authors: Guo Zhong Tao, Diana M Toivola, Qin Zhou, Pavel Strnad, Jian Liao, Kok Sun Looi, Yuquan Wei, Aida Habtezion, Bishr M OmaryAbstract:Absence or mutation of Keratins 8 (K8) or 18 (K18) cause predisposition to liver injury and apoptosis. We assessed the mechanisms of hepatocyte Keratin-mediated cytoprotection by comparing the protein expression profiles of livers from wild-type and K8-null mice using two-dimensional differential-in-gel-electrophoresis (2D-DIGE) and mass spectrometry. Prominent among the alterations were those of mitochondrial proteins, which were confirmed using 2D-DIGE of purified mitochondria. Ultrastructural analysis showed that mitochondria of livers that lack or have disrupted Keratins are significantly smaller than mitochondria of wild-type livers. Immunofluorescence staining showed irregular distribution of mitochondria in Keratin-absent or Keratin-mutant livers. K8-null livers have decreased ATP content; and K8-null mitochondria have less cytochrome c, increased release of cytochrome c after exposure to Ca2+ and oxidative stimulation, and a higher sensitivity to Ca2+-induced permeability transition. Therefore, Keratins play a direct or indirect role in regulating the shape and function of mitochondria. The effects of Keratin mutation on mitochondria are likely to contribute to hepatocyte predisposition to apoptosis and oxidative injury, and to play a pathogenic role in Keratin-mutation-related human liver disease.
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new consensus nomenclature for mammalian Keratins
Journal of Cell Biology, 2006Co-Authors: Jürgen Schweizer, Birgitte E Lane, Lutz Langbein, Thomas M. Magin, Bishr M Omary, David A D Parry, Pierre A Coulombe, Paul Edward Bowden, Lois J Maltais, Michael A. RogersAbstract:Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the Keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel Keratin genes and their encoded proteins. Their naming could not be adequately handled in the context of the original system. We propose a new consensus nomenclature for Keratin genes and proteins that relies upon and extends the 1982 system and adheres to the guidelines issued by the Human and Mouse Genome Nomenclature Committees. This revised nomenclature accommodates functional genes and pseudogenes, and although designed specifically for the full complement of human Keratins, it offers the flexibility needed to incorporate additional Keratins from other mammalian species.
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Keratins as susceptibility genes for end stage liver disease
Gastroenterology, 2005Co-Authors: Joseph K Lim, David A D Parry, Sheri M Krams, Carlos O Esquivel, Emmet B Keeffe, Teresa L Wright, Bishr M OmaryAbstract:Background & Aims: Keratins 8 and 18 protect the liver from stress. Keratin 8 and 18 variants in 17 of 467 liver disease explants and 2 of 349 blood bank controls were previously reported in 5 analyzed exonic regions. We asked whether mutations were present in the remaining 10 exons of Keratins 8 and 18. Methods: Exonic regions were polymerase chain reaction–amplified from genomic DNA, isolated from the above-mentioned 2 cohorts, and analyzed for the presence of mutations. Mutant Keratins were also studied biochemically. Results: We identified 10 novel Keratin 8 and 18 heterozygous variants in 44 of 467 explants and 11 of 349 controls: Keratin 18 deletion (Δ64–71), a Keratin 8 frameshift that truncates the last 14 amino acids; 8 missense Keratin 8 and 18 alterations; and several new polymorphisms. The most common variant, Keratin 8 R340H, at the highly conserved R340 was found in 30 of 467 explants and 10 of 349 controls (P = .02) and was confirmed in the diseased livers by generation of an R340H-specific antibody. Germline transmission and variant protein expression were verified. The mutations involved a variety of liver diseases, and some variants had an ethnic background preponderance. Mutations that introduced disulfide bonds (Keratin 8 G61C or R453C) decreased Keratin solubility, particularly after oxidative stress, whereas others decreased Keratin 8 phosphorylation (Keratin 8 G433S). Conclusions: The overall frequency of Keratin 8 and 18 variants was 12.4% in 467 liver disease explants and 3.7% in 349 blood bank controls (P
