The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform

Donald W Jacobsen - One of the best experts on this subject based on the ideXlab platform.

Bernhard LÜscher - One of the best experts on this subject based on the ideXlab platform.

  • Targeting of the transcription factor Max during apoptosis: phosphorylation-regulated cleavage by caspase-5 at an unusual Glutamic Acid Residue in position P1.
    The Biochemical journal, 2001
    Co-Authors: Anja Krippner-heidenreich, Robert V. Talanian, Renate Sekul, Regine Kraft, Hubert Thole, Holger Ottleben, Bernhard LÜscher
    Abstract:

    Max is the central component of the Myc/Max/Mad network of transcription factors that regulate growth, differentiation and apoptosis. Whereas the Myc and Mad genes and proteins are highly regulated, Max expression is constitutive and no post-translational regulation is known. We have found that Max is targeted during Fas-induced apoptosis. Max is first dephosphorylated and subsequently cleaved by caspases. Two specific cleavage sites for caspases in Max were identified, one at IEVE(10) decreasing S and one at SAFD(135) decreasing G near the C-terminus, which are cleaved in vitro by caspase-5 and caspase-7 respectively. Mutational analysis indicates that both sites are also used in vivo. Thus Max represents the first caspase-5 substrate. The unusual cleavage after a Glutamic Acid Residue is observed only with full-length, DNA-binding competent Max protein but not with corresponding peptides, suggesting that structural determinants might be important for this activity. Furthermore, cleavage by caspase-5 is inhibited by the protein kinase CK2-mediated phosphorylation of Max at Ser-11, a previously mapped phosphorylation site in vivo. These findings suggest that Fas-mediated dephosphorylation of Max is required for cleavage by caspase-5. The modifications that occur on Max in response to Fas signalling affect the DNA-binding activity of Max/Max homodimers. Taken together, our findings uncover three distinct processes, namely dephosphorylation and cleavage by caspase-5 and caspase-7, that target Max during Fas-mediated apoptosis, suggesting the regulation of the Myc/Max/Mad network through its central component.

  • Targeting of the transcription factor Max during apoptosis: phosphorylation-regulated cleavage by caspase-5 at an unusual Glutamic Acid Residue in position P1
    Biochemical Journal, 2001
    Co-Authors: Anja Krippner-heidenreich, Robert V. Talanian, Renate Sekul, Regine Kraft, Hubert Thole, Holger Ottleben, Bernhard LÜscher
    Abstract:

    Max is the central component of the Myc/Max/Mad network of transcription factors that regulate growth, differentiation and apoptosis. Whereas the Myc and Mad genes and proteins are highly regulated, Max expression is constitutive and no post-translational regulation is known. We have found that Max is targeted during Fas-induced apoptosis. Max is first dephosphorylated and subsequently cleaved by caspases. Two specific cleavage sites for caspases in Max were identified, one at IEVE10↓S and one at SAFD135↓G near the C-terminus, which are cleaved in vitro by caspase-5 and caspase-7 respectively. Mutational analysis indicates that both sites are also used in vivo. Thus Max represents the first caspase-5 substrate. The unusual cleavage after a Glutamic Acid Residue is observed only with full-length, DNA-binding competent Max protein but not with corresponding peptides, suggesting that structural determinants might be important for this activity. Furthermore, cleavage by caspase-5 is inhibited by the protein kinase CK2-mediated phosphorylation of Max at Ser-11, a previously mapped phosphorylation site in vivo. These findings suggest that Fas-mediated dephosphorylation of Max is required for cleavage by caspase-5. The modifications that occur on Max in response to Fas signalling affect the DNA-binding activity of Max/Max homodimers. Taken together, our findings uncover three distinct processes, namely dephosphorylation and cleavage by caspase-5 and caspase-7, that target Max during Fas-mediated apoptosis, suggesting the regulation of the Myc/Max/Mad network through its central component.

Jurgen Schweizer - One of the best experts on this subject based on the ideXlab platform.

  • a variable monilethrix phenotype associated with a novel mutation glu402lys in the helix termination motif of the type ii hair keratin hhb1
    Journal of Investigative Dermatology, 1998
    Co-Authors: Hermelita Winter, Christine Labreze, Valerie Chapalain, Jean Etienne Surlevebazeille, Michel Mercier, Michael A Rogers, Alain Taieb, Jurgen Schweizer
    Abstract:

    Monilethrix is a rare human hair disorder with autosomal dominant transmission that can be caused by mutations in hair keratins. Up until now, pathogenic mutations in the type II hair cortex keratins hHb6 and hHb1 were restricted to a highly conserved Glutamic Acid Residue Glu413 (Glu117 of the 2B subdomains) in the EIATYRRLLEGEE helix termination motif of the two keratins. The critical Glutamic Acid Residue was substituted either by a lysine or, less frequently, by an aspartic Acid Residue. Here we report a novel mutation in a French monilethrix family, which again consists of a lysine substitution of another highly conserved Glutamic Acid Residue, Glu402 (Glu106 of the 2B subdomain), in the EIATYRRLLEGEE motif of hHb1. Family members bearing the hHb1 Glu402Lys mutation exhibit a particularly variable disease phenotype. The pedigree comprises two infant members, one with pronounced dystrophic alopecia, follicular keratosis, and clear-cut moniliform hair, and one with no hair loss at all and moniliform hair detectable only by electron microscopy, as well as an adult individual without any clinically or electron microscopically detectable symptoms, but with clear historical proof of the disease.

  • a new mutation in the type ii hair cortex keratin hhb1 involved in the inherited hair disorder monilethrix
    Human Genetics, 1997
    Co-Authors: Hermelita Winter, Michael A Rogers, Mathias Gebhardt, Uwe Wollina, Lionell Boxall, David Chitayat, Riyana Babulhirji, Howard P Stevens, Abreham Zlotogorski, Jurgen Schweizer
    Abstract:

    Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved Glutamic Acid Residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding Glutamic Acid Residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.

Erica L Wright - One of the best experts on this subject based on the ideXlab platform.

Edward V Quadros - One of the best experts on this subject based on the ideXlab platform.