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The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light.

Heather Dehlin Scoma | Monica Humby | Geetha Yadav | Qingjiong Zhang | Joseph Fogerty | Joseph C Besharse
PloS one | 2011

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.

Pubmed ID: 21966515

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NEI NIH HHS, United States
    Id: EY02414
  • Agency: NEI NIH HHS, United States
    Id: P30-EY01931
  • Agency: NEI NIH HHS, United States
    Id: EY03222
  • Agency: NEI NIH HHS, United States
    Id: P30 EY001931
  • Agency: NEI NIH HHS, United States
    Id: R01 EY003222
  • Agency: NEI NIH HHS, United States
    Id: T32-EY014537
  • Agency: NEI NIH HHS, United States
    Id: T32 EY014537
  • Agency: NEI NIH HHS, United States
    Id: R01 EY002414

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