2lxw

Structural highlights

Function

XAF1_HUMAN 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 mitochondra, 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.^{[1] [2] [3] [4] [5]}

References

1. ↑ Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, Tamai K, Craig CG, McBurney MW, Korneluk RG. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol. 2001 Feb;3(2):128-33. PMID:11175744 doi:10.1038/35055027
2. ↑ Leaman DW, Chawla-Sarkar M, Vyas K, Reheman M, Tamai K, Toji S, Borden EC. 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. Epub 2002 May 23. PMID:12029096 doi:10.1074/jbc.M204851200
3. ↑ Xia Y, Novak R, Lewis J, Duckett CS, Phillips AC. 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. Epub 2006 Jan 24. PMID:16432762 doi:10.1007/s11010-005-9094-2
4. ↑ Arora V, Cheung HH, Plenchette S, Micali OC, Liston P, Korneluk RG. Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex. J Biol Chem. 2007 Sep 7;282(36):26202-9. Epub 2007 Jul 5. PMID:17613533 doi:M700776200
5. ↑ Straszewski-Chavez SL, Visintin IP, Karassina N, Los G, Liston P, Halaban R, Fadiel A, Mor G. 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. Epub 2007 Feb 28. PMID:17329253 doi:10.1074/jbc.M609038200