Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol

被引：0
作者：
Christian T. Hellwig
M. Eugenia Delgado
Josip Skoko
Lydia Dyck
Carol Hanna
Alexa Wentges
Claudia Langlais
Cathrin Hagenlocher
Alexandra Mack
David Dinsdale
Kelvin Cain
Marion MacFarlane
Markus Rehm
机构：
[1] Royal College of Surgeons in Ireland,Department of Physiology and Medical Physics
[2] Royal College of Surgeons in Ireland,Centre for Systems Medicine
[3] Institute of Cell Biology and Immunology,Biochemical Pharmacology, Department of Biology
[4] University of Stuttgart,undefined
[5] Stuttgart Research Center Systems Biology,undefined
[6] University of Stuttgart,undefined
[7] University of Konstanz,undefined
[8] MRC Toxicology Unit,undefined
[9] Stuttgart Center for Simulation Science (SC SimTech),undefined
[10] University of Stuttgart,undefined
来源：
Cell Death & Differentiation | 2022年 / 29卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Cancer cells that are resistant to Bax/Bak-dependent intrinsic apoptosis can be eliminated by proteasome inhibition. Here, we show that proteasome inhibition induces the formation of high molecular weight platforms in the cytosol that serve to activate caspase-8. The activation complexes contain Fas-associated death domain (FADD) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Furthermore, the complexes contain TRAIL-receptor 2 (TRAIL-R2) but not TRAIL-receptor 1 (TRAIL-R1). While RIPK1 inhibition or depletion did not affect proteasome inhibitor-induced cell death, TRAIL-R2 was found essential for efficient caspase-8 activation, since the loss of TRAIL-R2 expression abrogated caspase processing, significantly reduced cell death, and promoted cell re-growth after drug washout. Overall, our study provides novel insight into the mechanisms by which proteasome inhibition eliminates otherwise apoptosis-resistant cells, and highlights the crucial role of a ligand-independent but TRAIL-R2-dependent activation mechanism for caspase-8 in this scenario.
引用
收藏
页码：147 / 155
页数：8
相关论文
共 228 条
  • [1] Salvesen GS(1999)Caspase activation: the induced-proximity model Proc Natl Acad Sci USA 96 10964-7
  • [2] Dixit VM(2017)Caspase-8: regulating life and death Immunol Rev 277 76-89
  • [3] Tummers B(1995)FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis Cell 81 505-12
  • [4] Green DR(2003)Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis J Biol Chem 278 25534-41
  • [5] Chinnaiyan AM(2017)Initiation and execution mechanisms of necroptosis: an overview Cell Death Differ 24 1184-95
  • [6] O’Rourke K(2011)The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs Mol Cell 43 432-48
  • [7] Tewari M(2011)cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms Mol Cell 43 449-63
  • [8] Dixit VM(2014)Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis Science 345 98-101
  • [9] Harper N(2014)RIPK1 promotes death receptor-independent caspase-8-mediated apoptosis under unresolved ER stress conditions Cell death Dis 5 e1555-97
  • [10] Hughes M(2011)Proteasome inhibition can induce an autophagy-dependent apical activation of caspase-8 Cell Death Differ 18 1584-97
12345678910