X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling.
X-linked inhibitor of apoptosis protein (XIAP) is a potent suppressor of apoptotic cell death, which functions by directly inhibiting caspases, the principal effectors of apoptosis. Here we report that XIAP can also function as a cofactor in the regulation of gene expression by transforming growth factor-beta (TGF-beta). XIAP, but not the related proteins c-IAP1 or c-IAP2, associated with several members of the type I class of the TGF-beta receptor superfamily and potentiated TGF-beta-induced signaling. Although XIAP-mediated activation of c-Jun N-terminal kinase and nuclear factor kappa B was found to require the TGF-beta signaling intermediate Smad4, the ability of XIAP to suppress apoptosis was found to be Smad4-independent. These data implicate a role for XIAP in TGF-beta-mediated signaling that is distinct from its anti-apoptotic functions.
Birkey Reffey
S
S
Metabolism Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Wurthner
J U
JU
Parks
W T
WT
Roberts
A B
AB
Duckett
C S
CS
D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*; D051636:X-Linked Inhibitor of Apoptosis Protein
D011506:Proteins; D016212:Transforming Growth Factor beta; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human