The Experts below are selected from a list of 15153 Experts worldwide ranked by ideXlab platform
Stuart H Orkin - One of the best experts on this subject based on the ideXlab platform.
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the ubiquitous subunit of erythroid transcription factor nf e2 is a small basic Leucine Zipper protein related to the v maf oncogene
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Nancy C Andrews, Hediye Erdjumentbromage, Paul Tempst, K J Kotkow, Paul A Ney, Stuart H OrkinAbstract:Abstract Erythroid transcription factor NF-E2 is a tissue-restricted heterodimeric protein which recognizes an extended AP-1 motif [(T/C)TGCTGA(C/G)TCA(T/C)] found in the upstream locus control regions of the alpha- and beta-globin gene clusters. A cDNA clone encoding a cell-type-specific subunit of NF-E2, designated p45 NF-E2, has previously been characterized and shown to encode a basic-Leucine Zipper DNA-binding protein. Here we describe protein purification and cloning of cDNA that encodes the second basic-Leucine Zipper subunit of the native NF-E2 heterodimer. This polypeptide, designated p18, is widely expressed. It displays extensive homology to the v-maf oncogene product and a human retinal-specific protein, NRL. Unusual features in the basic region shared by v-Maf, NRL, and p18 place them in a distinct subfamily of AP-1-like proteins.
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erythroid transcription factor nf e2 is a haematopoietic specific basic Leucine Zipper protein
Nature, 1993Co-Authors: Nancy C Andrews, Hediye Erdjumentbromage, Mark B Davidson, Paul Tempst, Stuart H OrkinAbstract:Expression of globin genes in developing erythroid cells is controlled by upstream locus control regions. Activity of these regions in vivo requires an erythroid-specific nuclear factor (NF-E2) that binds AP-1-like recognition sites. Its tissue-specific component (p45 NF-E2) has been characterized by complementary DNA cloning as a new basic region–Leucine Zipper protein which dimerizes with a ubiquitous partner to form native NF-E2.
Derek S Welsbie - One of the best experts on this subject based on the ideXlab platform.
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targeted disruption of dual Leucine Zipper kinase and Leucine Zipper kinase promotes neuronal survival in a model of diffuse traumatic brain injury
Molecular Neurodegeneration, 2019Co-Authors: Derek S Welsbie, Amit K Patel, Nikolaos K Ziogas, Leyan Xu, Yusong Ge, Mohamed Lehar, Athanasios S Alexandris, Nicholas Stewart, Donald J ZackAbstract:Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual Leucine Zipper kinase (DLK) and Leucine Zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy. Moreover, we showed that DLK and LZK are the major upstream triggers for JUN N-terminal kinase (JNK) signaling following total axonal transection. However, the degree to which DLK/LZK are involved in TAI/TBI is unknown. Here we used the impact acceleration (IA) model of diffuse TBI, which produces TAI in the visual system, and complementary genetic and pharmacologic approaches to disrupt DLK and LZK, and explored whether DLK and LZK play a role in RGC perikaryal and axonal degeneration in response to TAI. Our findings show that the IA model activates DLK/JNK/JUN signaling but, in contrast to axotomy, many RGCs are able to recover from the injury and terminate the activation of the pathway. Moreover, while DLK disruption is sufficient to suppress JUN phosphorylation, combined DLK and LZK inhibition is required to prevent RGC cell death. Finally, we show that the FDA-approved protein kinase inhibitor, sunitinib, which has activity against DLK and LZK, is able to produce similar increases in RGC survival. The mitogen-activated kinase kinase kinases (MAP3Ks), DLK and LZK, participate in cell death signaling of CNS neurons in response to TBI. Moreover, sustained pharmacologic inhibition of DLK is neuroprotective, an effect creating an opportunity to potentially translate these findings to patients with TBI.
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enhanced functional genomic screening identifies novel mediators of dual Leucine Zipper kinase dependent injury signaling in neurons
Neuron, 2017Co-Authors: Derek S Welsbie, Katherine L Mitchell, Vinod Jaskularanga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit K PatelAbstract:Dual Leucine Zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify Leucine Zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs. Moreover, we identify four transcription factors, JUN, activating transcription factor 2 (ATF2), myocyte-specific enhancer factor 2A (MEF2A), and SRY-Box 11 (SOX11), as being the major downstream mediators through which DLK/LZK activation leads to RGC cell death. Increased understanding of the DLK pathway has implications for understanding and treating neurodegenerative diseases.
Nancy C Andrews - One of the best experts on this subject based on the ideXlab platform.
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the ubiquitous subunit of erythroid transcription factor nf e2 is a small basic Leucine Zipper protein related to the v maf oncogene
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Nancy C Andrews, Hediye Erdjumentbromage, Paul Tempst, K J Kotkow, Paul A Ney, Stuart H OrkinAbstract:Abstract Erythroid transcription factor NF-E2 is a tissue-restricted heterodimeric protein which recognizes an extended AP-1 motif [(T/C)TGCTGA(C/G)TCA(T/C)] found in the upstream locus control regions of the alpha- and beta-globin gene clusters. A cDNA clone encoding a cell-type-specific subunit of NF-E2, designated p45 NF-E2, has previously been characterized and shown to encode a basic-Leucine Zipper DNA-binding protein. Here we describe protein purification and cloning of cDNA that encodes the second basic-Leucine Zipper subunit of the native NF-E2 heterodimer. This polypeptide, designated p18, is widely expressed. It displays extensive homology to the v-maf oncogene product and a human retinal-specific protein, NRL. Unusual features in the basic region shared by v-Maf, NRL, and p18 place them in a distinct subfamily of AP-1-like proteins.
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erythroid transcription factor nf e2 is a haematopoietic specific basic Leucine Zipper protein
Nature, 1993Co-Authors: Nancy C Andrews, Hediye Erdjumentbromage, Mark B Davidson, Paul Tempst, Stuart H OrkinAbstract:Expression of globin genes in developing erythroid cells is controlled by upstream locus control regions. Activity of these regions in vivo requires an erythroid-specific nuclear factor (NF-E2) that binds AP-1-like recognition sites. Its tissue-specific component (p45 NF-E2) has been characterized by complementary DNA cloning as a new basic region–Leucine Zipper protein which dimerizes with a ubiquitous partner to form native NF-E2.
Mitsuyasu Hasebe - One of the best experts on this subject based on the ideXlab platform.
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involvement of auxin and a homeodomain Leucine Zipper i gene in rhizoid development of the moss physcomitrella patens
Development, 2003Co-Authors: Keiko Sakakibara, Rumiko Kofuji, Naomi Sumikawa, Takashi Murata, Tomoaki Nishiyama, Mitsuyasu HasebeAbstract:Differentiation of epidermal cells is important for plants because they are in direct contact with the environment. Rhizoids are multicellular filaments that develop from the epidermis in a wide range of plants, including pteridophytes, bryophytes, and green algae; they have similar functions to root hairs in vascular plants in that they support the plant body and are involved in water and nutrient absorption. In this study, we examined mechanisms underlying rhizoid development in the moss, Physcomitrella patens , which is the only land plant in which high-frequency gene targeting is possible. We found that rhizoid development can be split into two processes: determination and differentiation. Two types of rhizoids with distinct developmental patterns (basal and mid-stem rhizoids) were recognized. The development of basal rhizoids from epidermal cells was induced by exogenous auxin, while that of mid-stem rhizoids required an unknown factor in addition to exogenous auxin. Once an epidermal cell had acquired a rhizoid initial cell fate, expression of the homeodomain-Leucine Zipper I gene Pphb7 was induced. Analysis of Pphb7 disruptant lines showed that Pphb7 affects the induction of pigmentation and the increase in the number and size of chloroplasts, but not the position or number of rhizoids. This is the first report on the involvement of a homeodomain-Leucine Zipper I gene in epidermal cell differentiation.
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isolation of homeodomain Leucine Zipper genes from the moss physcomitrella patens and the evolution of homeodomain Leucine Zipper genes in land plants
Molecular Biology and Evolution, 2001Co-Authors: Keiko Sakakibara, Tomoaki Nishiyama, Masahiro Kato, Mitsuyasu HasebeAbstract:Homeobox genes encode transcription factors involved in many aspects of developmental processes. The homeodomain-Leucine Zipper (HD-Zip) genes, which are characterized by the presence of both a homeodomain and a Leucine Zipper motif, form a clade within the homeobox superfamily and were previously reported only from vascular plants. Here we report the isolation of 10 HD-Zip genes (named PPHB:1-PPHB:10) from the moss Physcomitrella patens. Based on a phylogenetic analysis of the 10 PPHB: genes and previously reported vascular plant HD-Zip genes, all of the PPHB: genes except Pphb3 belong to three of the four HD-Zip subfamilies (HD-Zip I, II, and III), indicating that these subfamilies originated before the divergence of the vascular plant and moss lineages. Pphb3 is sister to the HD-Zip II subfamily and has some distinctive characteristics, including the difference of the a(1) and d(1) sites of its Leucine Zipper motif, which are well conserved in each HD-Zip subfamily. Comparison of the genetic divergence of representative HD-Zip I and II genes showed that the evolutionary rate of HD-Zip I genes was faster than that of HD-Zip II genes.
Amit K Patel - One of the best experts on this subject based on the ideXlab platform.
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targeted disruption of dual Leucine Zipper kinase and Leucine Zipper kinase promotes neuronal survival in a model of diffuse traumatic brain injury
Molecular Neurodegeneration, 2019Co-Authors: Derek S Welsbie, Amit K Patel, Nikolaos K Ziogas, Leyan Xu, Yusong Ge, Mohamed Lehar, Athanasios S Alexandris, Nicholas Stewart, Donald J ZackAbstract:Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traumatic axonal injury (TAI), which often leads to axonal and sometimes perikaryal degeneration of CNS neurons. We have previously used genome-scale, arrayed RNA interference-based screens in primary mouse retinal ganglion cells (RGCs) to identify a pair of related kinases, dual Leucine Zipper kinase (DLK) and Leucine Zipper kinase (LZK) that are key mediators of cell death in response to simple axotomy. Moreover, we showed that DLK and LZK are the major upstream triggers for JUN N-terminal kinase (JNK) signaling following total axonal transection. However, the degree to which DLK/LZK are involved in TAI/TBI is unknown. Here we used the impact acceleration (IA) model of diffuse TBI, which produces TAI in the visual system, and complementary genetic and pharmacologic approaches to disrupt DLK and LZK, and explored whether DLK and LZK play a role in RGC perikaryal and axonal degeneration in response to TAI. Our findings show that the IA model activates DLK/JNK/JUN signaling but, in contrast to axotomy, many RGCs are able to recover from the injury and terminate the activation of the pathway. Moreover, while DLK disruption is sufficient to suppress JUN phosphorylation, combined DLK and LZK inhibition is required to prevent RGC cell death. Finally, we show that the FDA-approved protein kinase inhibitor, sunitinib, which has activity against DLK and LZK, is able to produce similar increases in RGC survival. The mitogen-activated kinase kinase kinases (MAP3Ks), DLK and LZK, participate in cell death signaling of CNS neurons in response to TBI. Moreover, sustained pharmacologic inhibition of DLK is neuroprotective, an effect creating an opportunity to potentially translate these findings to patients with TBI.
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enhanced functional genomic screening identifies novel mediators of dual Leucine Zipper kinase dependent injury signaling in neurons
Neuron, 2017Co-Authors: Derek S Welsbie, Katherine L Mitchell, Vinod Jaskularanga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit K PatelAbstract:Dual Leucine Zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify Leucine Zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs. Moreover, we identify four transcription factors, JUN, activating transcription factor 2 (ATF2), myocyte-specific enhancer factor 2A (MEF2A), and SRY-Box 11 (SOX11), as being the major downstream mediators through which DLK/LZK activation leads to RGC cell death. Increased understanding of the DLK pathway has implications for understanding and treating neurodegenerative diseases.