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Control of WHITE COLLAR localization by phosphorylation is a critical step in the circadian negative feedback process
Author(s) -
Cha Joonseok,
Chang ShwuShin,
Huang Guocun,
Cheng Ping,
Liu Yi
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.245
Subject(s) - biology , circadian rhythm , phosphorylation , collar , microbiology and biotechnology , negative feedback , process (computing) , negative control , neuroscience , computer science , physics , quantum mechanics , voltage , mechanical engineering , medicine , traditional medicine , engineering , operating system
Reversible protein phosphorylation has critical functions in the eukaryotic circadian negative feedback loops. In Neurospora , the FREQUENCY protein closes the circadian negative feedback loop by promoting the phosphorylation of its transcription activator, the WHITE COLLAR complex (WCC) and consequently inhibiting WCC activity. Here we show that protein phosphatase 4 is a novel component of the Neurospora clock by regulating both processes of the circadian negative feedback loop. The disruption of pp4 results in short period rhythms with low amplitude. In addition to its role in regulating FRQ phosphorylation and stability, PP4 also dephosphorylates and activates WCC. In contrast to PP2A, another phosphatase that activates WCC, PP4 has a major function in promoting nuclear entry of WCC. PKA, a WC kinase, inhibits WC nuclear localization. Furthermore, the FRQ‐dependent WC phosphorylation promotes WCC cytosolic localization. Together, these results revealed WCC nucleocytoplasmic shuttling as an important step in the circadian negative feedback process and delineated the FRQ‐dependent WCC inhibition as a two‐step process: the inhibition of WCC DNA‐binding activity followed by sequestration of WCC into the cytoplasm.