CAVIN-3 regulates negative limb protein complexes of the mammalian circadian oscillator

Diplôme Thèse CAVIN-3 regulates negative limb protein complexes of the mammalian circadian oscillator eng 2012-07-11 author Schneider Kim 563617 director Schibler Ulrich 22687 10.13097/archive-ouverte/unige:22002 urn:nbn:ch:unige-220026 Sc. 4451 The molecular circadian oscillators in mammals rely on a negative feedback loop involving the transcriptional repressors PER1, PER2, CRY1 and CRY2. Here we report the identification of CAVIN-3 as a novel, cytoplasmic PER2-interacting protein. We found that cellular CAVIN-3 levels directly influenced circadian clock properties. Loss- and gain-of-function of CAVIN-3 thus shortened and lengthened, respectively, the circadian period in fibroblasts. CAVIN-3 had a marked effect on the abundance of PER and CRY proteins, which were increased and decreased upon CAVIN-3 depletion and overexpression, respectively, and probably on the strength of the PER:CRY interaction, as suggested by mammalian two-hybrid assays. A CAVIN-3 variant carrying a mutated binding site for the previously reported interacting protein, Protein Kinase C (PKC) δ, failed to alter circadian period length. The role of CAVIN-3 in the clockwork may thus at least in part be mediated by its interaction with yet uncharacterized protein kinases. Cavin-3 Caveolin-1 Mammalian circadian gene expression Period 2-interacting proteins PER:CRY interaction Period length Dewey 570 43 Département de biologie moléculaire 161 false 5c4c40b9-246a-45ee-943d-3c54ddec720a Thesis Restricted Kim_Schneider_thesis_final.pdf 17958935 application/pdf 697c1876a13d962a9f692b903826813d8d22d464c3bb693b5931d6c6cd082767 restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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CAVIN-3 regulates negative limb protein complexes of the mammalian circadian oscillator				2012	1,013	38

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Schneider, Kim