Faculty, Staff and Student Publications

Publication Date

1-17-2025

Journal

iScience

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

DOI

10.1016/j.isci.2024.111603

PMID

39834856

PMCID

PMC11743101

PubMedCentral® Posted Date

12-15-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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