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The E3 Ligases Spsb1 and Spsb4 Regulate RevErb? Degradation and Circadian Period.

ABSTRACT: The time-dependent degradation of core circadian clock proteins is essential for the proper functioning of circadian timekeeping mechanisms that drive daily rhythms in gene expression and, ultimately, an organism's physiology. The ubiquitin proteasome system plays a critical role in regulating the stability of most proteins, including the core clock components. Our laboratory developed a cell-based functional screen to identify ubiquitin ligases that degrade any protein of interest and have started screening for those ligases that degrade circadian clock proteins. This screen identified Spsb4 as a putative novel E3 ligase for RevErb?. In this article, we further investigate the role of Spsb4 and its paralogs in RevErb? stability and circadian rhythmicity. Our results indicate that the paralogs Spsb1 and Spsb4, but not Spsb2 and Spsb3, can interact with and facilitate RevErb? ubiquitination and degradation and regulate circadian clock periodicity.

SUBMITTER: Mekbib T

PROVIDER: S-EPMC7953592 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The E3 Ligases Spsb1 and Spsb4 Regulate RevErbα Degradation and Circadian Period.

Mekbib Tsedey T Suen Ting-Chung TC Rollins-Hairston Aisha A DeBruyne Jason P JP

Journal of biological rhythms 20191014 6

The time-dependent degradation of core circadian clock proteins is essential for the proper functioning of circadian timekeeping mechanisms that drive daily rhythms in gene expression and, ultimately, an organism's physiology. The ubiquitin proteasome system plays a critical role in regulating the stability of most proteins, including the core clock components. Our laboratory developed a cell-based functional screen to identify ubiquitin ligases that degrade any protein of interest and have star ...[more]

PMID: 31607207

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