Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis
AUTOR(ES)
Qiu, Xiao-Bo
FONTE
Nature Publishing Group
RESUMO
Degradation of certain inhibitor of apoptosis proteins (IAPs) appears to be critical in the initiation of apoptosis, but the factors that regulate their degradation in mammalian cells are unknown. Nrdp1/FLRF is a RING finger-containing ubiquitin ligase that catalyzes degradation of the EGF receptor family member, ErbB3. We show here that Nrdp1 associates with BRUCE/apollon, a 530 kDa membrane-associated IAP, which contains a ubiquitin-carrier protein (E2) domain. In the presence of an exogenous E2, UbcH5c, purified Nrdp1 catalyzes BRUCE ubiquitination. In vivo, overexpression of Nrdp1 promotes ubiquitination and proteasomal degradation of BRUCE. In many cell types, apoptotic stimuli induce proteasomal degradation of BRUCE (but not of XIAP or c-IAP1), and decreasing Nrdp1 levels by RNA interference reduces this loss of BRUCE. Furthermore, decreasing BRUCE content by RNA interference or overexpression of Nrdp1 promotes apoptosis. Thus, BRUCE normally inhibits apoptosis, and Nrdp1 can be important in the initiation of apoptosis by catalyzing ubiquitination and degradation of BRUCE.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=380992Documentos Relacionados
- Melanoma inhibitor of apoptosis protein (ML-IAP) is a target for immune-mediated tumor destruction
- BRUCE, a Giant E2/E3 Ubiquitin Ligase and Inhibitor of Apoptosis Protein of the trans-Golgi Network, Is Required for Normal Placenta Development and Mouse Survival
- The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development
- Steve Bruce, um sociólogo em defesa da teoria da secularização
- Inhibition of interleukin 1β-converting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP