XIAP-associated factor 1

Definition:

Seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family. Inhibits anti-caspase activity of BIRC4. Induces cleavage and inactivation of BIRC4 independent of caspase activation. Mediates TNF-alpha-induced apoptosis and is involved in apoptosis in trophoblast cells. May inhibit BIRC4 indirectly by activating the mitochondrial apoptosis pathway. After translocation to mitochondria, promotes translocation of BAX to mitochondria and cytochrome c release from mitochondria. Seems to promote the redistribution of BIRC4 from the cytoplasm to the nucleus, probably independent of BIRC4 inactivation which seems to occur in the cytoplasm. The BIRC4-XAF1 complex mediates down-regulation of BIRC5/survivin; the process requires the E3 ligase activity of BIRC4. Seems to be involved in cellular sensitivity to the proapoptotic actions of TRAIL. May be a tumor suppressor by mediating apoptosis resistance of cancer cells.

References:

[1]. P Liston, et al. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol. 2001 Feb;3(2):128-33. [Content Brief]

[2]. Vinay Arora, et al. Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex. J Biol Chem. 2007 Sep 7;282(36):26202-9. [Content Brief]

[3]. Yan Xia, et al. Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP. Mol Cell Biochem. 2006 Jun;286(1-2):67-76. [Content Brief]

[4]. Douglas W Leaman, et al. Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. J Biol Chem. 2002 Aug 9;277(32):28504-11. [Content Brief]

[5]. Shawn L Straszewski-Chavez, et al. XAF1 mediates tumor necrosis factor-alpha-induced apoptosis and X-linked inhibitor of apoptosis cleavage by acting through the mitochondrial pathway. J Biol Chem. 2007 Apr 27;282(17):13059-72. [Content Brief]

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