Revisiting phosphoregulation of Cdc25C during M-phase induction

Year: 2024

Type: article

Abstract: Cdc25C undergoes a sudden and substantial gel mobility shift at M-phase onset, correlating with abrupt activation of both Cdc25C and Cdk1 activities. A positive feedback loop between Cdk1 and Cdc25C has been used to explain this hallmark phenomenon. Here, we demonstrate that the M-phase supershift and robust activation of Cdc25C are due to the site-comprehensive phosphorylation of its long intrinsically disordered regulatory domain without requiring Cdk1 or other major mitotic kinase activities. The phosphorylation process involves substrate-mediated assembly of phosphorylation machinery that catalyzes multisite phosphorylation continuously without substrate dissociation. In contrast to the site-comprehensive phosphorylation of Cdc25C occurring at M-phase onset, the site-specific phosphorylation of Cdc25C by Cdk1 or other major mitotic kinases generates slight gel mobility shifts and modest activation of Cdc25C prior to M-phase onset. These findings suggest a two-stage framework consisting of site-specific phosphorylation followed by site-comprehensive phosphorylation for Cdc25C regulation during M-phase induction.

Source: iScience

DOI: 10.1016/j.isci.2024.111603

Authors: Tan Tan, Chuanfen Wu, Ruoning Wang, Bih-Fang Pan, David Hawke, Fumin Yin, Zehao Su, Boye Liu, Sue-Hwa Lin, Wei Zhang, Jian Kuang

Institutions: The University of Texas MD Anderson Cancer Center, University of South China, Beijing Normal University

Language: English

Topic: Microtubule and mitosis dynamics

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,150

Funders: U.S. Department of Defense, Cancer Prevention and Research Institute of Texas, Natural Science Foundation of Hunan Province, National Institutes of Health, National Cancer Institute, DOD Prostate Cancer Research Program

OpenAlex ID: W4405414070