SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins

Luca Busino, Florian Bassermann, Alessio Maiolica, Choogon Lee, Patrick M. Nolan, Sofia I.H. Godinho, Giulio F. Draetta, Michele Pagano

Research output: Contribution to journalArticlepeer-review

410 Scopus citations

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 languageEnglish (US)
Pages (from-to)900-904
Number of pages5
JournalScience
Volume316
Issue number5826
DOIs
StatePublished - May 11 2007
Externally publishedYes

ASJC Scopus subject areas

  • General

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