AUTHOR=Li Pan , Liu Xueqin , Hao Zhimin , Jia Yanrong , Zhao Xiangdong , Xie Debao , Dong Jingao , Zeng Fanli 

TITLE=Dual Repressive Function by Cip1, a Budding Yeast Analog of p21, in Cell-Cycle START Regulation

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01623

DOI=10.3389/fmicb.2020.01623

ISSN=1664-302X

ABSTRACT=<p>Cip1, a newly identified yeast analog of p21, is a Cln3-CDK inhibitor that negatively regulates cell-cycle START. However, its function remains poorly understood. In this study, we found that deletion of <italic>CLN3</italic> did not result in bypass of G1-phase arrest caused by Cip1 overexpression. Cip1 depletion in <italic>cln3</italic>-null mutants significantly advanced the timing of Cln2 expression, supporting the idea that Cip1 represses START in a Cln3-independent manner. We set to search for novel Cip1 interacting proteins and found that Ccr4, a known START regulator, and its associated factor Caf120, interact with Cip1. Ccr4-Caf120 acts redundantly with Cdk1-Cln3 to inhibit Whi5-mediated regulation of START. This interaction was conserved between human Ccr4 and p21. In addition, deletion of <italic>WHI5</italic> robustly suppressed G1-phase arrest caused by Cip1 overexpression. We conclude that Cip1 negatively regulates START by acting as a dual repressor of Ccr4 in parallel with Cln3.</p>