One component of the circadian clock in mammals is the Clock-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 SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) 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.

SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins / L. Busino, F. Bassermann, A. Maiolica, C. Lee, P.M. Nolan, S.I. Godinho, G.F. Draetta, M. Pagano. - In: SCIENCE. - ISSN 0036-8075. - 316:5826(2007 May 11), pp. 900-904. [10.1126/science.1141194]

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

A. Maiolica;
2007-05-11

Abstract

One component of the circadian clock in mammals is the Clock-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 SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/52395
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