S phase cyclin-CDK specificity in ordering cell cycle phosphorylation

Abstract

Cell proliferation is an essential process in all organisms. Through a series of growth and division, the cell passes its genetic material to the next generation of cells. The molecular machinery that governs timing and execution of these events is called cyclin-dependent kinase (CDK). CDK is activated by multiple cyclins and phosphorylates hundreds of proteins associated with the cell cycle. The specificity of phosphorylation is partly dictated by recognition sequences on proteins called docking motifs that bind specific cyclins. These docking motifs create a plethora of barcodes that allow CDK to recognize and differentially phosphorylate many targets. In this work, a novel S-phase specific docking motif NLxxxL present in CDK inhibitory protein Far1 was mapped and the contribution of cyclin and Cks1 docking on Far1 degradation was analyzed. In estonian: Rakkude jagunemine on hädavajalik, sest see on aluseks geneetilise materjali ülekandeks järgmisesse rakkude põlvkonda. Rakutsüklit reguleerivad tsükliinist sõltuvad kinaasid (CDK), mis fosforüleerivad sadu substraatvalke, mis viivad läbi erinevaid rakutsükli sündmuseid. CDK substraatide fosforüleerimises mängivad olulist rolli tsükliinid, mis seonduvad kindlate motiividega substraatvalkudes. Need motiivid võimaldavad CDK kompleksil erinevatel ajahetkedel rakutsükli jooksul fosforüleerida sadu erinevaid valke. Käesolevas töös kirjeldati uus S-faasi CDK spetsiifiline tsükliin-substraat seondumismotiiv NLxxxL ning uuriti erinevate mehhanismide olulisust substraatide fosforüleerimisel.