The proteasome deubiquitinase inhibitor b-AP15 enhances DR5 activation-induced apoptosis through stabilizing DR5.

ABSTRACT: b-AP15 and its derivatives block proteasome deubiquitinase (DUB) activity and have been developed and tested in the clinic as potential cancer therapeutic agents. b-AP15 induces apoptosis in cancer cells, but the underlying mechanisms are largely undefined. The current study focuses on studying the modulatory effects of b-AP15 on death receptor 5 (DR5) levels and DR5 activation-induced apoptosis as well as on understanding the underlying mechanisms. Treatment with b-AP15 potently increased DR5 levels including cell surface DR5 in different cancer cell lines with limited or no effects on the levels of other related proteins including DR4, c-FLIP, FADD, and caspase-8. b-AP15 substantially slowed the degradation of DR5, suggesting that it stabilizes DR5. Moreover, b-AP15 effectively augmented

SUBMITTER: Oh YT 

PROVIDER: S-EPMC5556018 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature