Caspase-10-Mediated Heat Shock Protein 90β Cleavage Promotes UVB Irradiation-Induced Cell Apoptosis

Abstract

Heat shock protein 90β (Hsp90β) is involved in many cellular functions. However, the posttranslational modification of Hsp90β, especially in response to apoptotic stimulation, is not well understood. In this study, we found that Hsp90β 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 Hsp90β at D278, P293, and D294. The downregulation of Hsp90β mediated by caspase-8-dependent caspase-10 activation promoted UVB-induced cell apoptosis.

ACKNOWLEDGMENTS

We thank Junying Yuan (Harvard Medical School) for caspase-12 plasmid, Dean G. Tang and Michael Andreeff (University of Texas M. D. Anderson Cancer Center) for caspase-8-deficient Jurkat T cells, Didier Picard (Université de Genève) for p2HG/hHsp90β, Emad Alnemri (Thomas Jefferson University) for pKS-Rev-caspase-6, Seiji Kondo (M. D. Anderson Cancer Center) for pCDN3.1caspase-8, Bingliang Fang (M. D. Anderson Cancer Center) for pCDN3.1+caspase-3, and Jin Wang (Baylor College of Medicine) for pCDN3.1caspase-10. We thank Ann Sutton for critical reading of the manuscript.

This work was supported by the Pediatric Brain Tumor Foundation (Z.L.), a Brain Tumor Society research grant (Z.L.), a Phi Beta Psi Sorority research grant (Z.L.), an institutional research grant from the University of Texas M. D. Anderson Cancer Center (Z.L.), and National Cancer Institute grant 5R01CA109035 (Z.L.).