Registration Number
0225U004342,
(0121U109973)
, R & D reports
Title
Peculiarities of functional activity of ribosomal protein S6 (S6K1) kinase isoforms and molecular mechanisms of its regulation in normal and pathology
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Аналіз експресії та кореляції між експресією різних ізоформ S6K1 та патоморфологічними характеристиками пухлин простати з акцентом на агресивність (інвазивність, метастатичний потенціал) пухлин. Аналіз змін в стані ключових сигнальних каскадів залучених до злоякісної трансформації з застосуванням модельних клітин MCF7, з диференційною експресією ізоформ S6K1. Аналіз стану фосфорилюванння, як показник активності відомих субстратів S6K1 за наявності фосфоспецифічних антитіл з метою виявлення ізоформо специфічних субстратів. Дослідити вплив СоАлювання на активність S6K1. Біоінформатичний аналіз інтерактому RBPs із мРНК S6К1 білку та визначення розташування знайдених RBPs вздовж взаємодіючій мРНК.
Head
Filonenko Valerii V., д.б.н.
Registration Date
01-12-2025
Organization
Institute of Molecular Biology and Genetics of NAS of Ukraine
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Determination and characterization of features of functional activity and molecular mechanisms of its regulation of known isoforms of ribosomal protein kinase S6K1 - p55, p60, p70, p85 in normal and malignant transformation of cells.
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The object of the study is ribosomal protein kinase S6 isoforms.
The purpose of the work is to determine the features of the functional activity of ribosomal protein kinase S6 isoforms -S6K1 in normal and pathological conditions.
Research methods - CRISPR/Cas9 genome editing system and shRNA interference, gene expression analysis by real-time PCR, Western blot analysis of protein expression and their phosphorylation, immunocytochemistry and confocal microscopy.
The expression analysis and correlation between the expression of different S6K1 isoforms and pathomorphological characteristics of thyroid tumors were performed with an emphasis on the aggressiveness (invasiveness, metastatic potential) of tumors. According to the results of real-time PCR data analysis, a correlation was established between the expression of p60 of the S6K1 isoform and the invasiveness of tumors. The analysis of the state of key signaling cascades involved in malignant transformation using MCF7 model cells with differential expression of S6K1 isoforms was performed. A previously unknown connection was established between mTOR/S6K1 signaling and signaling cascades dependent on the activity of AKT1, AMPK, PKC, and PKA, which are also involved in the regulation of locomotor functions of cells. The effect of CoAlylation on S6K1 activity was studied. It was found that CoAlylation of Cys217 has a negative effect on the already activated form of S6K1, thereby confirming the existence of a new type of regulation of signaling molecules by CoAlylation. A bioinformatic analysis of the interactome of RBPs with S6K1 protein mRNA was performed
Product Description
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Antonina I. Khoruzhenko
Liliia O. Savinska
Harifulin Oleh M.
Iryna О. Tykhonkova
Alla P. Pohribna
Iryna V. Krupska
Vasyl I. Bobyk
Olha H. Vihontina
Liudmyla F. Yakovenko
Oksana М. Malanchuk
Serhii S. Palchevskyi
Oleksandr М. Skorokhod
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2025-12-01
