Cyclins & CDK Substrate Choice

Eukaryotic cell division is driven by cyclin-dependent kinases (CDKs). Distinct cyclin-CDK complexes are specialized to drive different cell cycle events, though the key molecular differences are only partly understood. We found that some CDK substrates, such as Ste5, contain a novel docking sequence that is recognized only by specific G1 cyclins and not by later S- or M-phase cyclins. These sequences are called “LP motifs” for their enrichment in Leu and Pro residues. They are analogous to previous “RXL” motifs, but the two types are recognized by distinct cyclin types and hence drive cyclin-specific phosphorylation. We are currently probing key sequence features of LP motifs, conducting proteome-wide analyses of LP-dependent interactions, and investigating how cyclins became functionally diversified during evolution. Collectively, these studies are illuminating how variation in both substrate docking and intrinsic potency of cyclins helps shape the CDK-substrate network.

Relevant Publications

Bhaduri S, Pryciak PM. Cyclin-specific docking motifs promote phosphorylation of yeast signaling proteins by G1/S Cdk complexes. Curr Biol. 2011 Oct 11;21(19):1615-23. doi: 10.1016/j.cub.2011.08.033. Epub 2011 Sep 22. PMID: 21945277; PMCID: PMC3196376.

Bhaduri S, Valk E, Winters MJ, Gruessner B, Loog M, Pryciak PM. A docking interface in the cyclin Cln2 promotes multi-site phosphorylation of substrates and timely cell-cycle entry. Curr Biol. 2015 Feb 2;25(3):316-325. doi: 10.1016/j.cub.2014.11.069. Epub 2015 Jan 22. PMID: 25619768; PMCID: PMC4318751.

Bandyopadhyay S, Bhaduri S, Örd M, Davey NE, Loog M, Pryciak PM. Comprehensive Analysis of G1 Cyclin Docking Motif Sequences that Control CDK Regulatory Potency In Vivo. Curr Biol. 2020 Nov 16;30(22):4454-4466.e5. doi: 10.1016/j.cub.2020.08.099. Epub 2020 Sep 24. PMID: 32976810; PMCID: PMC8009629.