NDLI: Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1)

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Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1)

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fang, Yanshan Sathyanarayanan, Sriram Sehgal, Amita
Description	Country affiliation: United States Author Affiliation: Fang Y ( Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.)
Abstract	Phosphorylation is an important timekeeping mechanism in the circadian clock that has been closely studied at the level of the kinases involved but may also be tightly controlled by phosphatase action. Here we demonstrate a role for protein phosphatase 1 (PP1) in the regulation of the major timekeeping molecules in the Drosophila clock, TIMELESS (TIM) and PERIOD (PER). Flies with reduced PP1 activity exhibit a lengthened circadian period, reduced amplitude of behavioral rhythms, and an altered response to light that suggests a defect in the rising phase of clock protein expression. On a molecular level, PP1 directly dephosphorylates TIM and stabilizes it in both S2R(+) cells and clock neurons. However, PP1 does not act in a simple antagonistic manner to SHAGGY (SGG), the kinase that phosphorylates TIM, because the behavioral phenotypes produced by inhibiting PP1 in flies are different from those achieved by overexpressing SGG. PP1 also acts on PER, and TIM regulates the control of PER by PP1, although it does not affect PP2A action on PER. We propose a modified model for post-translational regulation of the Drosophila clock, in which PP1 is critical for the rhythmic abundance of TIM/PER while PP2A also regulates the nuclear translocation of TIM/PER.
File Format	HTM / HTML
ISSN	08909369
e-ISSN	15495477
Journal	Genes & Development
Issue Number	12
Volume Number	21
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2007-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Molecular Discipline Biology__semicolon__developmental Discipline Biology__semicolon__genetics__semicolon__cell Discipline Biology Circadian Rhythm Physiology Drosophila Phosphoprotein Phosphatases Metabolism Animals Animals, Genetically Modified Binding Sites Brain Genetics Drosophila Proteins Genes, Insect Intracellular Signaling Peptides And Proteins Models, Biological Neurons Nuclear Proteins Period Circadian Proteins Phosphorylation Protein Phosphatase 1 Protein Processing, Post-translational Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Genetics Developmental Biology

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Role of phosphorylation in the mammalian circadian clock.

PERspective on PER phosphorylation.

Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1)

Balance between DBT/CKIepsilon kinase and protein phosphatase activities regulate phosphorylation and stability of Drosophila CLOCK protein.

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A master CLOCK hard at work brings rhythm to the transcriptome.

Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1)

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