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

Overview

Journal J Biol Rhythms

Date 2019 Oct 15

PMID 31607207

Citations 1

Authors

Tsedey Mekbib

Ting-Chung Suen

Aisha Rollins-Hairston

Jason P DeBruyne

Affiliations

Soon will be listed here.

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 RevErbα. In this article, we further investigate the role of Spsb4 and its paralogs in RevErbα stability and circadian rhythmicity. Our results indicate that the paralogs Spsb1 and Spsb4, but not Spsb2 and Spsb3, can interact with and facilitate RevErbα ubiquitination and degradation and regulate circadian clock periodicity.

Citing Articles

"The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism".

Mekbib T, Suen T, Rollins-Hairston A, Smith K, Armstrong A, Gray C PLoS Genet. 2022; 18(7):e1010305.

PMID: 35789210 PMC: 9286287. DOI: 10.1371/journal.pgen.1010305.

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