Abstract:
:We describe a mechanism by which the anti-apoptotic B cell lymphoma 2 (Bcl-2) protein is downregulated to induce apoptosis. ARTS (Sept4_i2) is a tumor suppressor protein that promotes cell death through specifically antagonizing XIAP (X-linked inhibitor of apoptosis). ARTS and Bcl-2 reside at the outer mitochondrial membrane in living cells. Upon apoptotic induction, ARTS brings XIAP and Bcl-2 into a ternary complex, allowing XIAP to promote ubiquitylation and degradation of Bcl-2. ARTS binding to Bcl-2 involves the BH3 domain of Bcl-2. Lysine 17 in Bcl-2 serves as the main acceptor for ubiquitylation, and a Bcl-2 K17A mutant has increased stability and is more potent in protection against apoptosis. Bcl-2 ubiquitylation is reduced in both XIAP- and Sept4/ARTS-deficient MEFs, demonstrating that XIAP serves as an E3 ligase for Bcl-2 and that ARTS is essential for this process. Collectively, these results suggest a distinct model for the regulation of Bcl-2 by ARTS-mediated degradation.
journal_name
Cell Repjournal_title
Cell reportsauthors
Edison N,Curtz Y,Paland N,Mamriev D,Chorubczyk N,Haviv-Reingewertz T,Kfir N,Morgenstern D,Kupervaser M,Kagan J,Kim HT,Larisch Sdoi
10.1016/j.celrep.2017.09.052subject
Has Abstractpub_date
2017-10-10 00:00:00pages
442-454issue
2issn
2211-1247pii
S2211-1247(17)31342-6journal_volume
21pub_type
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