First Author | Bartke T | Year | 2004 |
Journal | Mol Cell | Volume | 14 |
Issue | 6 | Pages | 801-11 |
PubMed ID | 15200957 | Mgi Jnum | J:91044 |
Mgi Id | MGI:3045825 | Doi | 10.1016/j.molcel.2004.05.018 |
Citation | Bartke T, et al. (2004) Dual Role of BRUCE as an Antiapoptotic IAP and a Chimeric E2/E3 Ubiquitin Ligase. Mol Cell 14(6):801-11 |
abstractText | Apoptotic cell death and survival is controlled by pro- and antiapoptotic proteins. Because these proteins act on each other, cell fate is dictated by the relative activity of pro- versus antiapoptotic proteins. Here we report that BRUCE, a conserved 528 kDa peripheral membrane protein of the trans-Golgi network, protects cells against apoptosis and functions as an inhibitor of apoptosis (IAP). By using wild-type and mutant forms we show that BRUCE inhibits caspase activity and apoptosis depending on its BIR domain. Upon apoptosis induction, BRUCE is antagonized by three mechanisms: first, through binding to Smac; second, by the protease HtrA2; and third, by caspase-mediated cleavage. In addition to its IAP activity BRUCE has the distinctive property of functioning as a chimeric E2/E3 ubiquitin ligase with Smac being a substrate. Our work suggests that, owing to its two activities and its localization, BRUCE may function as a specialized regulator of cell death pathways. |