Zaets' I. The mechanism of expression, activity regulation and functional significance in a cell of the novel ribosomal protein S6 kinase isoform – p60-S6K1.

The thesis is devoted to the study of mechanisms of expression and regulation, and functional significance in a cell of the novel ribosomal protein S6 kinase 1 isoform - p60-S6K1. It was established that expression of p60-S6K1 can result from at least two different transcripts: the predominant S6K1 transcript via alternative translation using the third in-frame start codon and/or specific p60-S6K1 transcript. The data revealed that the p60-S6K1 isoform possesses kinase activity that can be either constitutive or mitogen-regulated depending on a cell type. Results demonstrated that p60-S6K1 is not subjected to phosphorylation on critical-for-kinase-activity sites Thr229 та Thr389 and, therefore, does not respond to mTORC1-dependent signaling. The p60-S6K1 isoform was shown to be able to exert positive effect on cell proliferation and migration in HEK-293 cells. It was revealed that p60-S6K1 can perform S6K1-independent function of initiation of the epithelial-mesenchymal transition in MCF-7 cells. The ratio of p60- and p70-S6K1 expression can be considered as a prospective diagnostic marker of cancer cells undergone the epithelial-mesenchymal transition.