Posttranscriptional downregulation of c- IAP2 by the ubiquitin protein ligase c- IAP1 in vivo.
Inhibitor of apoptosis proteins (IAPs) c- IAP1 and c- IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c- IAP1 and c- IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c- IAP1 in a physiologic setting, c- IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c- IAP1(-/-) mice do, however, express markedly elevated levels of c- IAP2 protein in the absence of increased c- IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-kappaB, resting and cytokine-induced NF-kappaB activation was not impaired in c- IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c- IAP1 revealed that c- IAP2 is a direct target for c- IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism.[1]References
- Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Conze, D.B., Albert, L., Ferrick, D.A., Goeddel, D.V., Yeh, W.C., Mak, T., Ashwell, J.D. Mol. Cell. Biol. (2005) [Pubmed]
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