Unknown

Dataset Information

0

Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression.


ABSTRACT: Using a forward genetics ENU mutagenesis screen for recessive mutations that affect circadian rhythmicity in the mouse, we isolated a long period (approximately 26 hr) circadian mutant named Overtime (Ovtm). Positional cloning and genetic complementation reveal that Ovtm is encoded by the F-box protein FBXL3, a component of the SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligase complex. The Ovtm mutation causes an isoleucine to threonine (I364T) substitution leading to a loss of function in FBXL3, which interacts specifically with the CRYPTOCHROME (CRY) proteins. In Ovtm mice, expression of the PERIOD proteins PER1 and PER2 is reduced; however, the CRY proteins CRY1 and CRY2 are unchanged. The loss of FBXL3 function leads to a stabilization of the CRY proteins, which in turn leads to a global transcriptional repression of the Per and Cry genes. Thus, Fbxl3(Ovtm) defines a molecular link between CRY turnover and CLOCK/BMAL1-dependent circadian transcription to modulate circadian period.

SUBMITTER: Siepka SM 

PROVIDER: S-EPMC3762874 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression.

Siepka Sandra M SM   Yoo Seung-Hee SH   Park Junghea J   Song Weimin W   Kumar Vivek V   Hu Yinin Y   Lee Choogon C   Takahashi Joseph S JS  

Cell 20070426 5


Using a forward genetics ENU mutagenesis screen for recessive mutations that affect circadian rhythmicity in the mouse, we isolated a long period (approximately 26 hr) circadian mutant named Overtime (Ovtm). Positional cloning and genetic complementation reveal that Ovtm is encoded by the F-box protein FBXL3, a component of the SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligase complex. The Ovtm mutation causes an isoleucine to threonine (I364T) substitution leading to a loss of function in FBXL3  ...[more]

Similar Datasets

| S-EPMC1323156 | biostudies-literature
| S-EPMC4157330 | biostudies-literature
| S-EPMC2952072 | biostudies-literature
| S-EPMC3606995 | biostudies-literature
| S-EPMC3411996 | biostudies-literature
| S-EPMC2666933 | biostudies-literature
| S-EPMC4791021 | biostudies-literature
| S-EPMC1502481 | biostudies-literature
| S-EPMC3708730 | biostudies-literature
| S-EPMC6377142 | biostudies-literature