Abstract:
:Post-translational processes are essential for the generation and dynamics of mammalian circadian rhythms. In particular, phosphorylation of the key circadian protein PER2 precisely controls the period and phase of circadian oscillations. However, the mechanisms underlying that control are poorly understood. Here, we identified in a high-throughput RNAi-based genetic screen casein kinase 2 (CK2) as a PER2-phosphorylating kinase and novel component of the mammalian circadian clock. When CK2 subunits are silenced by RNAi or when CK2 activity is inhibited pharmacologically, circadian rhythms are disrupted. CK2 binds to PER2 in vivo, phosphorylates PER2 specifically at N-terminal residues in vitro, and supports normal nuclear PER2 accumulation. Mutation of CK2 phosphorylation sites decreases PER2 stability and copies CK2 inhibition regarding oscillation dynamics. We propose a new concept of how PER2 phosphorylation and stabilization can set the clock speed in opposite directions, dependent on the phase of action.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Maier B,Wendt S,Vanselow JT,Wallach T,Reischl S,Oehmke S,Schlosser A,Kramer Adoi
10.1101/gad.512209subject
Has Abstractpub_date
2009-03-15 00:00:00pages
708-18issue
6eissn
0890-9369issn
1549-5477pii
23/6/708journal_volume
23pub_type
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