The IAP family: endogenous caspase inhibitors with multiple biological activities.
IAPs (inhibitors of apoptosis) are a family of proteins containing one or more characteristic BIR domains. These proteins have multiple biological activities that include binding and inhibiting caspases, regulating cell cycle progression, and modulating receptor-mediated signal transduction. Our recent studies found the IAP family members XIAP and c-IAP1 are ubiquitinated and degraded in proteasomes in response to apoptotic stimuli in T cells, and their degradation appears to be important for T cells to commit to death. In addition to three BIR domains, each of these IAPs also contains a RING finger domain. We found this region confers ubiquitin protease ligase (E3) activity to IAPs, and is responsible for the auto-ubiquitination and degradation of IAPs after an apoptotic stimulus. Given the fact that IAPs can bind a variety of proteins, such as caspases and TRAFs, it will be of interest to characterize potential substrates of the E3 activity of IAPs and the effects of ubiquitination by IAPs on signal transduction, cell cycle, and apoptosis.
Yang
Y L
YL
Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. yiliyang@box-y.nih.gov
Li
X M
XM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
D001426:Bacterial Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D014452:Ubiquitins; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; D020169:Caspases