Posttranslational mechanisms regulate the mammalian circadian clock
Posttranslational mechanisms regulate the mammalian circadian clock
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 (CKI) 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 CKI. We also provide in vivo evidence that casein kinase I delta is a second clock relevant kinase.
855-867
Lee, Choogon
f78d12c0-9160-4825-90b4-f5400e691f46
Etchegaray, Jean-Pierre
30d3f015-f289-4969-b58f-d3fc6ecd6707
Cagampang, Felino R.A.
7cf57d52-4a65-4554-8306-ed65226bc50e
Loudon, Andrew S.I.
8a8068a4-ed1d-49ec-b2ae-4170e00c039a
Reppert, Steven M.
49ca3b7a-e289-4c53-a4ff-e56cc34229de
2001
Lee, Choogon
f78d12c0-9160-4825-90b4-f5400e691f46
Etchegaray, Jean-Pierre
30d3f015-f289-4969-b58f-d3fc6ecd6707
Cagampang, Felino R.A.
7cf57d52-4a65-4554-8306-ed65226bc50e
Loudon, Andrew S.I.
8a8068a4-ed1d-49ec-b2ae-4170e00c039a
Reppert, Steven M.
49ca3b7a-e289-4c53-a4ff-e56cc34229de
Lee, Choogon, Etchegaray, Jean-Pierre, Cagampang, Felino R.A., Loudon, Andrew S.I. and Reppert, Steven M.
(2001)
Posttranslational mechanisms regulate the mammalian circadian clock.
Cell, 107 (7), .
(doi:10.1016/S0092-8674(01)00610-9).
Abstract
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 (CKI) 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 CKI. We also provide in vivo evidence that casein kinase I delta is a second clock relevant kinase.
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Published date: 2001
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Local EPrints ID: 25751
URI: http://eprints.soton.ac.uk/id/eprint/25751
ISSN: 0092-8674
PURE UUID: db37c5ad-a202-414c-bfe4-4f951a77de34
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Date deposited: 10 Apr 2006
Last modified: 16 Mar 2024 03:29
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Author:
Choogon Lee
Author:
Jean-Pierre Etchegaray
Author:
Andrew S.I. Loudon
Author:
Steven M. Reppert
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