| First Author | Edison N | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 2 | Pages | 442-454 |
| PubMed ID | 29020630 | Mgi Jnum | J:254214 |
| Mgi Id | MGI:6104164 | Doi | 10.1016/j.celrep.2017.09.052 |
| Citation | Edison N, et al. (2017) Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis. Cell Rep 21(2):442-454 |
| abstractText | 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. |
