Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis

The Journal of Cell Biology
Rachid MazrouiImed-Eddine Gallouzi

Abstract

The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is significantly reduced in the absence of pp32/PHAP-I. Substituting aspartate 226 with an alanine creates a noncleavable isoform of HuR that, when overexpressed, maintains its association with pp32/PHAP-I and delays the apoptotic response. Thus, we propose a model in which HuR association with pp32/PHAP-I and its caspase-mediated cleavage constitutes a regulatory step that contributes to an amplified apoptotic response.

References

Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·X C Fan, J A Steitz
Jan 8, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N SchiavoneS Capaccioli
Jan 11, 2000·Molecular and Cellular Biology·W WangM Gorospe
Feb 26, 2000·Carcinogenesis·S W Lowe, A W Lin
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·I E GallouziJ A Steitz
Apr 6, 2001·Cellular and Molecular Life Sciences : CMLS·C M Brennan, J A Steitz
May 23, 2002·Biochimie·Kelvin CainGerald M Cohen
Dec 5, 2002·Genes & Development·Michael KullmannLudger Hengst
Jun 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Krystyna Mazan-MamczarzMyriam Gorospe
Aug 29, 2003·The Journal of Biological Chemistry·Kate van der GiessenImed Eddine Gallouzi
Apr 23, 2004·The EMBO Journal·Michelle M HillSeamus J Martin
Feb 17, 2005·Nature Reviews. Molecular Cell Biology·Jerry E Chipuk, Douglas R Green
Apr 30, 2005·The EMBO Journal·Ashish LalMyriam Gorospe
Jun 7, 2005·Cell·Douglas R Green
Sep 2, 2005·Molecular and Cellular Biology·Yong Zhong XuDanuta Radzioch
Feb 14, 2006·Science·Saquib A LakhaniRichard A Flavell
Mar 8, 2006·The Journal of Cell Biology·Paul Anderson, Nancy Kedersha
May 9, 2006·Developmental Cell·Zachary T Schafer, Sally Kornbluth
Aug 22, 2006·Cancer Biology & Therapy·Kageaki KuribayashiWafik S El-Deiry
Dec 21, 2006·The Journal of Biological Chemistry·Barbara FriesJan Chemnitz
May 4, 2007·Molecular Biology of the Cell·Rachid MazrouiImed-Eddine Gallouzi
May 4, 2007·Molecular Biology of the Cell·Kate van der Giessen, Imed-Eddine Gallouzi
May 31, 2007·Cell Cycle·Kotb AbdelmohsenMyriam Gorospe

❮ Previous
Next ❯

Citations

Jun 27, 2008·Cellular and Molecular Life Sciences : CMLS·M N Hinman, H Lou
Jun 19, 2012·European Biophysics Journal : EBJ·Rafael Manfred ScheibaIrene Díaz-Moreno
Dec 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kotb AbdelmohsenMyriam Gorospe
Jun 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Patrick T ReillyTak Wah Mak
Apr 1, 2010·The Journal of Biological Chemistry·Christopher von Roretz, Imed-Eddine Gallouzi
Aug 3, 2010·The Journal of Biological Chemistry·Gillian L DruryImed-Eddine Gallouzi
Jun 8, 2011·The Journal of Biological Chemistry·Christopher von RoretzImed-Eddine Gallouzi
Jul 29, 2011·The Journal of Biological Chemistry·Sudha TalwarViswanathan Palanisamy
Jul 26, 2012·The Journal of Biological Chemistry·Natalia FilippovaL Burt Nabors
Aug 24, 2012·The Journal of Biological Chemistry·Alexa M DicksonJeffrey Wilusz
Jan 6, 2009·The Journal of Biological Chemistry·Wei PanXuejun Jiang
Apr 17, 2009·Molecular Biology of the Cell·Sophie MokasRachid Mazroui
Mar 25, 2009·Molecular and Cellular Biology·Vicky KatsanouDimitris L Kontoyiannis
May 8, 2009·American Journal of Physiology. Renal Physiology·Dina A AyupovaBeth S Lee
May 1, 2010·Cancer Cell International·Marie-Josée FournierRachid Mazroui
Mar 23, 2012·Molecular Cancer·Elisa LatorreAlessandro Provenzani
Jul 31, 2013·PloS One·Anna S SahlbergMarkus A Penttinen
Jun 28, 2014·Nature Communications·Anne CammasImed-Eddine Gallouzi
Aug 13, 2014·Medical Oncology·Ioly Kotta-LoizouStamatios Theocharis
Sep 19, 2014·Biogerontology·Danae Campos-MeloMichael J Strong
Apr 7, 2015·FEBS Letters·Antonio Díaz-QuintanaIrene Díaz-Moreno
May 2, 2014·FEBS Letters·Laure TwyffelsVéronique Kruys
Dec 29, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jean-Sébastien MaltaisMichel Grandbois
Jan 29, 2016·Nucleic Acids Research·Jiyoung KimMyriam Gorospe
Mar 15, 2012·Ageing Research Reviews·Wengong Wang
Oct 23, 2010·Pharmacology & Therapeutics·Antonio Paolo BeltramiCarlo Alberto Beltrami
Sep 22, 2011·Wiley Interdisciplinary Reviews. RNA·Kotb Abdelmohsen, Myriam Gorospe
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Christopher von RoretzImed-Eddine Gallouzi
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Jonathan R Brody, Gregory E Gonye
Aug 27, 2014·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Patrick T ReillyLishun Wang
Feb 15, 2011·Biochimica Et Biophysica Acta·Christopher von RoretzImed-Eddine Gallouzi
Apr 7, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·David Fernández-Ramos, María L Martínez-Chantar
Jun 10, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Sara Zamora-CaballeroJeronimo Bravo
Jul 13, 2012·Cancer Biology & Therapy·Danielle M PinedaJonathan R Brody
Aug 28, 2010·Journal of Nucleic Acids·Hyeon Ho KimMyriam Gorospe

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Methods Mentioned

BETA
flow cytometry
transfection
cleavage assay
pull-down
immunoprecipitation
PCR

Software Mentioned

Adobe
Photoshop
Axiovision

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