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Degradation of Survivin by the X-linked Inhibitor of Apoptosis (XIAP)-XAF1 Complex

Arora, Vinay ; Cheung, Herman H. ; Plenchette, Stéphanie ; Micali, O. Cristina ; Liston, Peter ; Korneluk, Robert G.

The Journal of biological chemistry, 2007-09, Vol.282 (36), p.26202-26209 [Periódico revisado por pares]

United States: Elsevier Inc

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Degradation of Survivin by the X-linked Inhibitor of Apoptosis (XIAP)-XAF1 Complex
Autor: Arora, Vinay ; Cheung, Herman H. ; Plenchette, Stéphanie ; Micali, O. Cristina ; Liston, Peter ; Korneluk, Robert G.
Assuntos: Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Antiviral Agents - pharmacology ; Apoptosis - drug effects ; Apoptosis - physiology ; Apoptosis Regulatory Proteins ; Baculoviral IAP Repeat-Containing 3 Protein ; Cell Line, Tumor ; Cysteine Proteinase Inhibitors - pharmacology ; Down-Regulation - drug effects ; Down-Regulation - physiology ; Humans ; Inhibitor of Apoptosis Proteins - genetics ; Inhibitor of Apoptosis Proteins - metabolism ; Interferon-beta - pharmacology ; Intracellular Signaling Peptides and Proteins ; Leupeptins - pharmacology ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Mitosis - drug effects ; Mitosis - physiology ; Multiprotein Complexes - genetics ; Multiprotein Complexes - metabolism ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neuronal Apoptosis-Inhibitory Protein - genetics ; Neuronal Apoptosis-Inhibitory Protein - metabolism ; Survivin ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Ubiquitin - genetics ; Ubiquitin - metabolism ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - metabolism ; X-Linked Inhibitor of Apoptosis Protein - genetics ; X-Linked Inhibitor of Apoptosis Protein - metabolism
É parte de: The Journal of biological chemistry, 2007-09, Vol.282 (36), p.26202-26209
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Descrição: X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a putative tumor suppressor in which expression is significantly reduced in human cancer cell lines and primary tumors. The proapoptotic effects of XAF1 have been attributed to both caspase-dependent and -independent means. In particular, XAF1 reverses the anti-caspase activity of XIAP, a physiological inhibitor of apoptosis. We further investigated the function of XAF1 by examining its relationship with other IAPs. Immunoprecipitation studies indicate that XAF1 binds to XIAP, cIAP1, cIAP2, Livin, TsIAP, and NAIP but not Survivin, an IAP that prevents mitotic catastrophe and in which antiapoptotic activity is exerted through direct XIAP interaction and stabilization. We found that overexpressed XAF1 down-regulates the protein expression of Survivin. Under these conditions, Survivin expression was restored in the presence of the proteasome inhibitor MG132 or a XIAP RING mutant that is defective in ubiquitin-protein isopeptide ligase (E3) activity, suggesting that XAF1 interaction activates E3 activity of XIAP and targets Survivin by direct ubiquitination. In addition, RNA interference targeting endogenous XIAP protected Survivin degradation by XAF1. Furthermore, interferon-β-mediated XAF1 induction promoted formation of an endogenous XIAP-XAF1-Survivin complex. This complex facilitated Survivin degradation, which was prevented in XAF1-/- stable clones. Altogether, our study demonstrates that XAF1 mediates Survivin down-regulation through a complex containing XIAP, supporting dual roles for XAF1 in apoptosis and mitotic catastrophe.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Degradation of Survivin by the X-linked Inhibitor of Apoptosis (XIAP)-XAF1 Complex

Arora, Vinay ; Cheung, Herman H. ; Plenchette, Stéphanie ; Micali, O. Cristina ; Liston, Peter ; Korneluk, Robert G.

United States: Elsevier Inc

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