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PMID: 17984062 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

beta-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 46 ·2007-11-13 ·Pages 18061-6

Boularan C, Scott MG, Bourougaa K, Bellal M, Esteve E, Thuret A, Benmerah A, Tramier M, Coppey-Moisan M, Labbé-Jullié C, Fåhraeus R, Marullo S

Abstract

beta-arrestins (beta-arrs), two ubiquitous proteins involved in serpentine heptahelical receptor regulation and signaling, form constitutive homo- and heterooligomers stabilized by inositol 1,2,3,4,5,6-hexakisphosphate (IP6). Monomeric beta-arrs are believed to interact with receptors after agonist activation, and therefore, beta-arr oligomers have been proposed to represent a resting biologically inactive state. In contrast to this, we report here that the interaction with and subsequent titration out of the nucleus of the protooncogene Mdm2 specifically require beta-arr2 oligomers together with the previously characterized nucleocytoplasmic shuttling of beta-arr2. Mutation of the IP6-binding sites impair oligomerization, reduce interaction with Mdm2, and inhibit p53-dependent antiproliferative effects of beta-arr2, whereas the competence for receptor regulation and signaling is maintained. These observations suggest that the intracellular concentration of beta-arr2 oligomers might control cell survival and proliferation.

MeSH Terms
Animals Arrestins/chemistry,physiology Binding Sites Biopolymers/chemistry COS Cells Cell Line Chlorocebus aethiops Humans Phytic Acid/metabolism,pharmacology Proto-Oncogene Proteins c-mdm2/physiology Tumor Suppressor Protein p53/antagonists & inhibitors beta-Arrestin 2 beta-Arrestins
Chemicals
ARRB2 protein, human Arrestins Biopolymers Tumor Suppressor Protein p53 beta-Arrestin 2 beta-Arrestins Phytic Acid MDM2 protein, human Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Boularan Cédric
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche 8104), 75014 Paris, France.
Scott Mark G H
Bourougaa Karima
Bellal Myriam
Esteve Emmanuel
Thuret Alain
Benmerah Alexandre
Tramier Marc
Coppey-Moisan Maité
Labbé-Jullié Catherine
Fåhraeus Robin
Marullo Stefano
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0705550104
Published
2007-11-13
Epub
2007-00-05
Pages
18061-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2084296
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0705550104 PMC Full Text View journal details
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