The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3- and caspase 9-interacting sites

The Journal of Cell Biology
John SilkeDavid L Vaux

Abstract

The X-linked mammalian inhibitor of apoptosis protein (XIAP) has been shown to bind several partners. These partners include caspase 3, caspase 9, DIABLO/Smac, HtrA2/Omi, TAB1, the bone morphogenetic protein receptor, and a presumptive E2 ubiquitin-conjugating enzyme. In addition, we show here that XIAP can bind to itself. To determine which of these interactions are required for it to inhibit apoptosis, we generated point mutant XIAP proteins and correlated their ability to bind other proteins with their ability to inhibit apoptosis. partial differential RING point mutants of XIAP were as competent as their full-length counterparts in inhibiting apoptosis, although impaired in their ability to oligomerize with full-length XIAP. Triple point mutants, unable to bind caspase 9, caspase 3, and DIABLO/HtrA2/Omi, were completely ineffectual in inhibiting apoptosis. However, point mutants that had lost the ability to inhibit caspase 9 and caspase 3 but retained the ability to inhibit DIABLO were still able to inhibit apoptosis, demonstrating that IAP antagonism is required for apoptosis to proceed following UV irradiation.

References

Jul 17, 1997·Nature·Q L DeverauxJ C Reed
May 9, 1998·The Journal of Biological Chemistry·R TakahashiJ C Reed
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G SannaR J Ulevitch
Feb 17, 1999·Genes & Development·Q L Deveraux, J C Reed
Feb 12, 2000·Molecular and Cellular Biology·R R HozakP D Friesen
Aug 10, 2000·The Journal of Biological Chemistry·C SunS W Fesik
Aug 22, 2000·The Journal of Biological Chemistry·S M SrinivasulaE S Alnemri
Feb 7, 2001·The Journal of Cell Biology·P G EkertD L Vaux
Mar 21, 2001·Cell·J ChaiP Dataa
Mar 21, 2001·Cell·S J RiedlG S Salvesen

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Citations

Jul 20, 2005·Cancer Chemotherapy and Pharmacology·Ahmad FariedHiroyuki Kuwano
Oct 9, 2007·Journal of Cancer Research and Clinical Oncology·Carsten KempkensteffenSteffen Weikert
Jun 23, 2011·Apoptosis : an International Journal on Programmed Cell Death·Bavat BornsteinSarit Larisch
Aug 4, 2007·Pharmaceutical Research·Marcello D'AmelioFrancesco Cecconi
May 6, 2003·Biochemical and Biophysical Research Communications·David L Vaux, John Silke
Jun 6, 2003·Journal of Molecular and Cellular Cardiology·Kelly M RegulaLorrie A Kirshenbaum
Mar 27, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Andréa C LeBlanc
Oct 24, 2003·Molecular and Cellular Neurosciences·Z ZhaoG M Pasinetti
Feb 15, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Inigo EspinosaJaime Prat
May 21, 2005·Nature Reviews. Cancer·Martin E Gleave, Brett P Monia
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·David L Vaux, John Silke
Sep 30, 2006·Cell Death and Differentiation·J Greenwood, J Gautier
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Aug 30, 2005·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Parco M SiuStephen E Alway
Apr 17, 2007·Annals of Surgery·Douglas J TurnerEric D Strauch
Aug 19, 2008·Genes & Development·Andrew J SchileHermann Steller
Jul 30, 2004·Molecular and Cellular Biology·John C WilkinsonColin S Duckett
Mar 6, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Eugene RoscioliPeter Zalewski
Apr 5, 2005·Immunopharmacology and Immunotoxicology·Ki-Chan HaSoo-Wan Chae
Jan 27, 2010·Expert Opinion on Therapeutic Patents·John A Flygare, Wayne J Fairbrother
Jun 4, 2004·Expert Opinion on Biological Therapy·Kim N Chi, Martin E Gleave
Feb 5, 2015·Biophysical Journal·Eloise MastrangeloMario Milani
Aug 19, 2007·Journal of Molecular Biology·Su-Chang LinHao Wu
Mar 28, 2007·Heart Failure Clinics·Luanda P Grazette, Anthony Rosenzweig
May 20, 2003·Immunological Reviews·Justine C Lee, Marcus E Peter
Jan 6, 2006·IUBMB Life·Ting NiFangdong Zou
Mar 1, 2012·IUBMB Life·Rebecca FelthamJohn Silke
Aug 24, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mónica Suárez KorsnesTore Aune
Apr 13, 2010·Cytokine·Dhan V KalvakolanuSudhakar Kalakonda
Jan 23, 2015·Toxicology Mechanisms and Methods·Radhakrishna SuraB Bhaskar Gollapudi

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Methods Mentioned

BETA
ubiquitination
nuclear magnetic resonance
immunoprecipitation
coimmunoprecipitation
transfection
FACS
PCR
irradiating

Software Mentioned

Freehand9

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