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

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Defense Thèse de doctorat : Univ. Genève, 2012 - Sc. 4451 - 2012/07/11
Abstract 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.
Keywords Cavin-3Caveolin-1Mammalian circadian gene expressionPeriod 2-interacting proteinsPER:CRY interactionPeriod length
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URN: urn:nbn:ch:unige-220026
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SCHNEIDER, Kim. CAVIN-3 regulates negative limb protein complexes of the mammalian circadian oscillator. Université de Genève. Thèse, 2012. https://archive-ouverte.unige.ch/unige:22002

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Deposited on : 2012-08-13

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