XIAP-associated factor 1 (BIRC4-binding protein, XAF1, BIRC4BP, XIAPAF1)
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Function
- seems to function as a negative regulator of members of the IAP protein/BIRC protein family
- inhibits anti-caspase activity of BIRC4
- induces cleavage & inactivation of BIRC4 independent of caspase activation
- mediates TNF-alpha-induced apoptosis & 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 & cytochrome c release from mitochondria
- seems to promote 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; 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
- interacts with BIRC4[1][3]; interaction is not detected[2]
- interacts with BIRC1, BIRC2, BIRC3, BIRC7 & BIRC8
- part of an complex consisting of BIRC4, XAF1 & BIRC5
- complex formation requires IFN-beta stimulation
Structure
contains 1 TRAF-type Zn+2 finger
Compartment
- cytoplasm. nucleus, mitochondrion
- found in the cytoplasm & nucleus of placental syncytiotrophoblasts
- translocates to mitochondria upon TNF-alpha treatment
- isoforms 1, 5: nucleus
Alternative splicing
named isoforms=7
Expression
- widely expressed
- isoform 5 is widely expressed
- expressed in placenta (at protein level)
- selectively expressed in third trimester placenta
- up-regulated by IFN-beta in cell lines sensitive to the proapoptotic effects of IFN-beta but not in apoptosis-resistant cells
- up-regulated by TNF-alhpa in trophoblast cells
Pathology
- expression is frequently down-regulated in cancer cell lines
More general terms
References
- ↑ 1.0 1.1 UniProt http://www.uniprot.org/uniprot/Q6GPH4.html
- ↑ 2.0 2.1 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: https://www.ncbi.nlm.nih.gov/pubmed/16432762
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/11175744