Browsing by Author "Leoshko, Valeriia"

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Deciphering the interaction of clustered phosphorylation sites in a multisite phosphorylation network – example of Ndd1 protein
(Tartu Ülikool, 2023) Leoshko, Valeriia; Valk, Ervin, juhendaja; Loog, Mart, juhendaja; Tartu Ülikool. Loodus- ja täppisteaduste valdkond; Tartu Ülikool. Tehnoloogiainstituut
Multisite phosphorylation is a vital cellular regulatory process. Cdk1, the master cell cycle regulator, forms a complex with cyclin and Cks1, activating Cdk1 and directing it to specific target proteins. Phosphorylation by Cdk1 occurs at serine or threonine residues followed by proline, with enhanced specificity in the presence of arginine or lysine at the +3 position. Cks1 and the Clb2 phosphate-binding pocket facilitate secondary phosphorylation in phosphorylation clusters that tend to form in intrinsically disordered protein regions, generating signalling specificity. This thesis focuses on Ndd1, a transcriptional co-activator essential for nuclear division. The involvement of Cks1 and the recently discovered Clb2 phosphate-binding pocket is critical for Ndd1 multisite phosphorylation. By investigating a specific phosphorylation cluster within Ndd1, this thesis aims to unravel the complex phosphorylation networks mediated by clustering, Cks1, and the Clb2 phosphate-binding pocket.
Degradation of budding yeast protein Far1 during G1/S phase transition
(2021) Leoshko, Valeriia
Cell cycle events must be precisely controlled for the cell to proliferate. Cyclin-dependent kinases (Cdks) upon activation by cyclins control cell cycle events. Cyclin-Cdk complexes govern events of cell cycle by binding their substrate proteins at specific docking motifs and phosphorylating them, thus changing the proteins’ activity. Far1 is a cyclin-dependent kinase inhibitor, that causes cell cycle arrest in response to mating pheromones. However, if mating pheromones are not present, Far1 is degraded. Clb5-Cdk1 complex phosphorylates the protein at S87/S91 residues, which triggers Far1 degradation. A Clb5-Cdk1 docking motif in N-terminal part of Far1 was recently discovered. This sequence, however, serves as docking motif only in truncated NFar1(1-170 aa). In this work it was shown that another possible motif involved in Far1 degradation might be located between 170th and 190th amino acids in the protein, Far1 does not contain another degron besides S87/S91 and Pho85 kinase does not affect Far1 degradation.