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Publication : Posttranslational mechanisms regulate the mammalian circadian clock.

First Author  Lee C Year  2001
Journal  Cell Volume  107
Issue  7 Pages  855-67
PubMed ID  11779462 Mgi Jnum  J:73655
Mgi Id  MGI:2156146 Doi  10.1016/s0092-8674(01)00610-9
Citation  Lee C, et al. (2001) Posttranslational mechanisms regulate the mammalian circadian clock. Cell 107(7):855-67
abstractText  We have examined posttranslational regulation of clock proteins in mouse liver in vivo. The mouse PERIOD proteins (mPER1 and mPER2), CLOCK, and BMAL1 undergo robust circadian changes in phosphorylation. These proteins, the cryptochromes (mCRY1 and mCRY2), and casein kinase I epsilon (CKIepsilon) form multimeric complexes that are bound to DNA during negative transcriptional feedback. CLOCK:BMAL1 heterodimers remain bound to DNA over the circadian cycle. The temporal increase in mPER abundance controls the negative feedback interactions. Analysis of clock proteins in mCRY-deficient mice shows that the mCRYs are necessary for stabilizing phosphorylated mPER2 and for the nuclear accumulation of mPER1, mPER2, and CKIepsilon. We also provide in vivo evidence that casein kinase I delta is a second clock relevant kinase.
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