Abstract
One component of the circadian clock in mammals is the Gock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCFFbxl3 ubiquitin ligase complex. This regulation by SCFFbxl3 is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2 -/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins.
Original language | English (US) |
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Pages (from-to) | 900-904 |
Number of pages | 5 |
Journal | Science |
Volume | 316 |
Issue number | 5826 |
DOIs | |
State | Published - May 11 2007 |
Externally published | Yes |
ASJC Scopus subject areas
- General