beta-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53.
Proc Natl Acad Sci U S A
; 104(46): 18061-6, 2007 Nov 13.
Article
em En
| MEDLINE
| ID: mdl-17984062
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Fítico
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Biopolímeros
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Proteína Supressora de Tumor p53
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Arrestinas
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Proteínas Proto-Oncogênicas c-mdm2
Limite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França