Cell cycle dependent nuclear localization

Abstract

Cell cycle is a sequence of precisely timed events, controlled mainly by the cyclin-dependent kinase (CDK) activity. CDK is activated by binding to another protein - cyclin and regulates the cellular processes via phosphorylation. One of the important tools in mediating enzyme activity is localization. Some proteins change their subcellular localization according to the cell cycle phase, for example, shuttle between the cytoplasm and nucleus, which is also mediated by CDK activity. Nucleocytoplasmic shuttling depends on the presence of the nuclear localization signal (NLS) and nuclear export signal (NES) in the target protein, and phosphoresidues can tune the activity of these signals. In this work, the role of CDK sites overlapping with bipartite NLS in Psy4 and Dna2 proteins was studied, and truncated localization modules that are sufficient for replicating the wild type proteins shuttling were identified. In estonian: Rakutsükkel on täpselt järjestatud sündmuste jada, mis on koordineeritud tsükliinist sõltuvate kinaaside (CDK) poolt. CDK on aktiivne vaid koos tsükliiniga ning vastav kompleks reguleeritud rakutsüklit valkude fosforüleerimise kaudu. Rakusisene paiknemine on oluline tegur valkude funktsioonide piiramisel. Mitmete valkude paiknemine muutub rakutsükli jooksul, näiteks transporditakse valke tuumast sisse ja välja CDK-vahendatud fosforüleerimise kaudu. Selleks on vajalikud tuuma impordi ja ekspordi signaalid, mille aktiivsust võib mõjutada nende fosforüleerimine. Käesolevas töös uuritakse, kuidas CDK reguleerib tuuma lokalisatsiooni mooduleid valkudes Psy4 ja Dna2.