Li Pan, Liu Xueqin, Hao Zhimin, Jia Yanrong, Zhao Xiangdong, Xie Debao, Dong Jingao, Zeng Fanli
College of Life Sciences, Hebei Agricultural University, Baoding, China.
State Key Laboratory of North China Crop Improvement and Regulation, Baoding, China.
Front Microbiol. 2020 Jul 9;11:1623. doi: 10.3389/fmicb.2020.01623. eCollection 2020.
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 did not result in bypass of G1-phase arrest caused by Cip1 overexpression. Cip1 depletion in -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 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.
Cip1是新发现的p21酵母类似物，是一种Cln3 - CDK抑制剂，对细胞周期起始点进行负调控。然而，其功能仍知之甚少。在本研究中，我们发现缺失 不会导致因Cip1过表达引起的G1期阻滞的旁路。在 - 缺失突变体中Cip1缺失显著提前了Cln2表达的时间，支持了Cip1以不依赖Cln3的方式抑制起始点的观点。我们着手寻找新的与Cip1相互作用的蛋白，发现已知的起始点调节因子Ccr4及其相关因子Caf120与Cip1相互作用。Ccr4 - Caf120与Cdk1 - Cln3共同作用抑制Whi5介导的起始点调节。这种相互作用在人类Ccr4和p21之间是保守的。此外，缺失 强烈抑制了由Cip1过表达引起的G1期阻滞。我们得出结论，Cip1通过与Cln3并行作为Ccr4的双重抑制因子来负调控起始点。
