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Nat Commun

Title:		A processive phosphorylation circuit with multiple kinase inputs and mutually diversional routes controls G1/S decision
Author(s):		Venta R; Valk E; Ord M; Kosik O; Paabo K; Maljavin A; Kivi R; Faustova I; Shtaida N; Lepiku M; Moll K; Doncic A; Koivomagi M; Loog M;
Address:		"Institute of Technology, University of Tartu, Tartu, 50411, Estonia. Department of Biology, Stanford University, Stanford, CA, 94305, USA. Institute of Technology, University of Tartu, Tartu, 50411, Estonia. mart.loog@ut.ee"
Journal Title:		Nat Commun
Year:		2020
Volume:		20200415
Issue:		1
Page Number:		1836 -
DOI:		10.1038/s41467-020-15685-z
ISSN/ISBN:		2041-1723 (Electronic) 2041-1723 (Linking)
Abstract:		"Studies on multisite phosphorylation networks of cyclin-dependent kinase (CDK) targets have opened a new level of signaling complexity by revealing signal processing routes encoded into disordered proteins. A model target, the CDK inhibitor Sic1, contains linear phosphorylation motifs, docking sites, and phosphodegrons to empower an N-to-C terminally directed phosphorylation process. Here, we uncover a signal processing mechanism involving multi-step competition between mutually diversional phosphorylation routes within the S-CDK-Sic1 inhibitory complex. Intracomplex phosphorylation plays a direct role in controlling Sic1 degradation, and provides a mechanism to sequentially integrate both the G1- and S-CDK activities while keeping S-CDK inhibited towards other targets. The competing phosphorylation routes prevent premature Sic1 degradation and demonstrate how integration of MAPK from the pheromone pathway allows one to tune the competition of alternative phosphorylation paths. The mutually diversional phosphorylation circuits may be a general way for processing multiple kinase signals to coordinate cellular decisions in eukaryotes"
Keywords:		"Blotting, Western Cell Division/genetics/physiology Cyclin-Dependent Kinases/genetics/metabolism Escherichia coli/genetics/metabolism G1 Phase/genetics/*physiology Immunoprecipitation Mass Spectrometry Phosphorylation S Phase/genetics/*radiation effects S;"
Notes:		"MedlineVenta, Rainis Valk, Ervin Ord, Mihkel Kosik, Oleg Paabo, Kaur Maljavin, Artemi Kivi, Rait Faustova, Ilona Shtaida, Nastassia Lepiku, Martin Moll, Kaidi Doncic, Andreas Koivomagi, Mardo Loog, Mart eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2020/04/17 Nat Commun. 2020 Apr 15; 11(1):1836. doi: 10.1038/s41467-020-15685-z"