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

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.
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https://www.hal.inserm.fr/inserm-00174967
Contributor : Stefano Marullo <>
Submitted on : Monday, January 14, 2008 - 10:07:56 AM
Last modification on : Wednesday, August 19, 2020 - 11:17:02 AM
Long-term archiving on: : Friday, November 25, 2016 - 5:05:10 PM

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Cédric Boularan, Mark Scott, Karima Bourougaa, Myriam Bellal, Emmanuel Esteve, et al.. beta-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2007, 104 (46), pp.18061-6. ⟨10.1073/pnas.0705550104⟩. ⟨inserm-00174967⟩

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