The De-Ubiquitinylating Enzyme, USP2, Is Associated with the Circadian Clockwork and Regulates Its Sensitivity to Light
Autor: | Joseph Fogerty, Heather Dehlin Scoma, Monica Humby, Joseph C. Besharse, Geetha Yadav, Qingjiong Zhang |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Male
Anatomy and Physiology Mouse Light Circadian clock Sensory Physiology lcsh:Medicine CLOCK Proteins Clockwork Social and Behavioral Sciences Polymerase Chain Reaction Behavioral Neuroscience Mice 0302 clinical medicine Molecular Cell Biology Psychology lcsh:Science Mice Knockout 0303 health sciences Multidisciplinary ARNTL Transcription Factors Suprachiasmatic nucleus Animal Models Period Circadian Proteins Sensory Systems Cell biology Circadian Rhythm Mental Health Liver Medicine Sensory Perception Female Suprachiasmatic Nucleus Ubiquitin-Specific Proteases Ubiquitin Thiolesterase Research Article Blotting Western Biology Neurological System Retina Cell Line 03 medical and health sciences Model Organisms Endopeptidases Animals Humans Immunoprecipitation Circadian rhythm 030304 developmental biology Computational Neuroscience lcsh:R Wild type Computational Biology Molecular biology Cellular Neuroscience NIH 3T3 Cells lcsh:Q Physiological Processes Chronobiology 030217 neurology & neurosurgery Neuroscience |
Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 9, p e25382 (2011) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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