CAVIN-3 regulates circadian period length and PER:CRY protein abundance and interactions.
In mammals, transcriptional autorepression by Period (PER) and Cryptochrome (CRY) protein complexes is essential for the generation of circadian rhythms. We have identified CAVIN-3 as a new, cytoplasmic PER2-interacting protein influencing circadian clock properties. Thus, CAVIN-3 loss- and gain-of-function shortened and lengthened, respectively, the circadian period in fibroblasts and affected PER:CRY protein abundance and interaction. While depletion of protein kinase Cδ (PKCδ), a known partner of CAVIN-3, had little effect on circadian gene expression, CAVIN-3 required the PKCδ-binding site to exert its effect on period length. This suggests the involvement of yet uncharacterized protein kinases. Finally, CAVIN-3 activity in circadian gene expression was independent of caveolae.
Department of Molecular Biology, Sciences III, University of Geneva, Geneva 1211, Switzerland.
Kim
K
Schneider
Thomas
T
Köcher
Teemu
T
Andersin
Teymuras
T
Kurzchalia
Ueli
U
Schibler
David
D
Gatfield
D000818:Animals; D021941:Caveolae / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics* / Q000502:physiology; D056931:Cryptochromes / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051745:Protein Kinase C-delta / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D016601:RNA-Binding Proteins
C505360:CAVIN3 protein, human; C112745:Cavin1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D016601:RNA-Binding Proteins; D051745:Protein Kinase C-delta