title: The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light.
abstract: 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.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Heather Dehlin
authors.initials: HD
authors.lastname: Scoma
authors.forename: Monica
authors.initials: M
authors.lastname: Humby
authors.forename: Geetha
authors.initials: G
authors.lastname: Yadav
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Joseph
authors.initials: J
authors.lastname: Fogerty
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Besharse
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics / Q000528:radiation effects; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008027:Light; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases
chemical_list: D056930:ARNTL Transcription Factors; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; C579224:Usp2 protein, mouse