title: Caspase-10-mediated heat shock protein 90 beta cleavage promotes UVB irradiation-induced cell apoptosis.
abstract: Heat shock protein 90 beta (Hsp90 beta) is involved in many cellular functions. However, the posttranslational modification of Hsp90 beta, especially in response to apoptotic stimulation, is not well understood. In this study, we found that Hsp90 beta was cleaved by activated caspase-10 under UVB irradiation. Caspase-10 activation, in turn, depended on caspase-8, which cleaved caspase-10 directly. Autocrine secretion of FAS ligand and upregulated FAS expression induced by UVB irradiation contributed to activation of caspase-10, which cleaved Hsp90 beta at D278, P293, and D294. The downregulation of Hsp90 beta mediated by caspase-8-dependent caspase-10 activation promoted UVB-induced cell apoptosis.
authors.affiliation: Department of Neuro-Oncology, Brain Tumor Center, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Hehua
authors.initials: H
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Dexing
authors.initials: D
authors.lastname: Fang
authors.forename: David
authors.initials: D
authors.lastname: Hawke
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053455:Caspase 10 / Q000235:genetics / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D053222:Fas Ligand Protein; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D009842:Oligopeptides; C470795:benzyloxycarbonyl-alanyl-glutamyl-valyl-aspartic acid fluoromethyl ketone; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D053455:Caspase 10; D053181:Caspase 8