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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Dev+Cell 2016 ; 37 (4): 337-49 Nephropedia Template TP
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The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis #MMPMID27219062
Goodall ML; Fitzwalter B; Zahedi S; Wu M; Rodriguez D; Mulcahy-Levy JM; Green DR; Morgan M; Cramer SD; Thorburn A
Dev Cell 2016[May]; 37 (4): 337-49 PMID27219062show ga
Although autophagy controls cell death and survival, underlying mechanisms are poorly understood and it is unknown if autophagy just affects whether or not cells die or also controls other aspects of programmed cell death. MAP3K7 is a tumor suppressor gene associated with poor disease-free survival in prostate cancer. Here we report that Map3k7 deletion in mouse prostate cells sensitizes to cell death by TNF-related apoptosis inducing ligand (TRAIL). Surprisingly, this death occurs primarily through necroptosis, not apoptosis, due to assembly of the necrosome in association with the autophagy machinery, mediated by p62/SQSTM1 recruitment of RIPK1. The mechanism of cell death switches to apoptosis if p62-dependent recruitment of the necrosome to the autophagy machinery is blocked. These data show that the autophagy machinery can control the mechanism of programmed cell death by serving as a scaffold rather than by degrading cargo.