The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PLoS One 2011;6(9):e25382
Date
10/04/2011Pubmed ID
21966515Pubmed Central ID
PMC3179520DOI
10.1371/journal.pone.0025382Scopus ID
2-s2.0-80053107902 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
We have identified a novel component of the circadian clock that regulates its sensitivity to light at the evening light to dark transition. USP2 (Ubiquitin Specific Protease 2), which de-ubiquitinylates and stabilizes target proteins, is rhythmically expressed in multiple tissues including the SCN. We have developed a knockout model of USP2 and found that exposure to low irradiance light at ZT12 increases phase delays of USP2(-/-) mice compared to wildtype. We additionally show that USP2b is in a complex with several clock components and regulates the stability and turnover of BMAL1, which in turn alters the expression of several CLOCK/BMAL1 controlled genes. Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes.
Author List
Scoma HD, Humby M, Yadav G, Zhang Q, Fogerty J, Besharse JCMESH terms used to index this publication - Major topics in bold
ARNTL Transcription FactorsAnimals
Blotting, Western
CLOCK Proteins
Cell Line
Circadian Rhythm
Endopeptidases
Female
Humans
Immunoprecipitation
Light
Liver
Male
Mice
Mice, Knockout
NIH 3T3 Cells
Period Circadian Proteins
Polymerase Chain Reaction
Retina
Suprachiasmatic Nucleus
Ubiquitin Thiolesterase
Ubiquitin-Specific Proteases
