Mutation of a PER2 phosphodegron perturbs the circadian phosphoswitch

• DOI: 10.1073/pnas.2000266117
• Publication Date: 2020-05-01T01:35:16Z
• Authors: Shusaku Masuda; Rajesh Narasimamu...; Hikari Yoshitane; Jae Kyoung Kim; Yoshitaka Fukada; David M. Virshup
• Keywords: PER2

Casein kinase 1 (CK1) plays a central role in regulating the period of circadian clock. In mammals, PER2 protein abundance is regulated by CK1-mediated phosphorylation and proteasomal degradation. On other hand, recent studies have questioned whether degradation core machinery critical step clock regulation. Prior cell-based found that CK1 at Ser478 recruits ubiquitin E3 ligase β-TrCP, leading to Creation this phosphodegron phosphoswitch also implicated temperature compensation. However, vivo evidence influences lacking. Here, we generated analyzed PER2-Ser478Ala knock-in mice. The mice showed longer behavioral analysis. Molecularly, mutant accumulated both nucleus cytoplasm mouse liver, while Per2 messenger RNA (mRNA) levels were minimally affected. Nuclear PER1, CRY1, CRY2 proteins increased, probably due stabilization PER2-containing complexes. embryonic fibroblasts derived from PER2-Ser478Ala::LUC mice, three-phase decay compensation was perturbed. These data provide direct for importance phosphorylation-regulated stability validate model.