Multisite phosphorylation by Cdk1 initiates delayed negative feedback to control mitotic transcription

• DOI: 10.1101/2021.02.14.431158
• Publication Date: 2021-02-15T05:30:14Z
• Authors: Jonathan B. Asfaha; Mihkel Örd; Christopher R. Ca...; Ilona Faustova; Mart Loog; David O. Morgan
• Keywords: Cyclin B; Cyclin B1; Polo-like kinase; Mitotic exit; Cyclin A

Summary Cell-cycle progression is driven by the phosphorylation of cyclin-dependent kinase (Cdk) substrates 1–3 . The order substrate depends in part on general rise Cdk activity during cell cycle 4–7 , together with variations docking to sites associated cyclin and Cks subunits 3, 6, 8–10 Many are modified at multiple provide more complex regulation 9, 11–14 Here, we describe an elegant regulatory circuit based multisite Ndd1, a transcriptional co-activator genes required for mitotic 15, 16 As cells enter mitosis, Ndd1 Cdk1 known promote ( CLB2 ) gene transcription, resulting positive feedback 17–20 Consistent these findings, show that low promotes expression entry. We also find, however, inhibited high levels arrest. Inhibition accompanied degradation, present evidence Cdk1-Clb2 generates phosphodegrons leading its degradation. Complete Clb2-Cdk1-Cks1 requires phosphothreonine-binding site Cks1, as well novel phosphate-binding pocket Clb2 21 therefore propose initial primes protein secondary phosphodegrons, degradation only activity. Together, our results suggest rising act first triggering rapid then promoting delayed negative feedback, pulse expression.