In:
Science, American Association for the Advancement of Science (AAAS), Vol. 316, No. 5826 ( 2007-05-11), p. 900-904
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.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.1141194
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2007
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
Permalink