2. Academic Validation
  3. Revisiting phosphoregulation of Cdc25C during M-phase induction

Revisiting phosphoregulation of Cdc25C during M-phase induction

  • iScience. 2024 Dec 15;28(1):111603. doi: 10.1016/j.isci.2024.111603.
Tan Tan 1 2,  Chuanfen Wu 1,  Ruoning Wang 1,  Bih-Fang Pan 3,  David Hawke 3,  Fumin Yin 4,  Zehao Su 4,  Boye Liu 5,  Sue-Hwa Lin 6,  Wei Zhang 4,  Jian Kuang 1
Affiliations

Affiliations

  • 1 Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • 2 Department of Biochemistry and Molecular Biology, University of South China, Hengyang, Hunan 421001, China.
  • 3 Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • 4 Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
  • 5 Key Laboratory for Biodiversity and Ecological Engineering of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
  • 6 Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
PMID: 39834856 DOI: 10.1016/j.isci.2024.111603
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.

Keywords

Biological sciences; Cell; Cell biology.

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