Abstract
Template activating factor-I (TAF-I) is a multifunctional protein involved in various biological processes including the inhibition of histone acetylation, DNA replication, cell cycle regulation, and oncogenesis. Two main TAF-I isoforms with different N-termini, TAF-Iα and TAF-Iβ (SET), are expressed in cells. There are numerous data about functional properties of TAF-Iβ, whereas the effects of TAF-Iα remain largely unexplored. Here, we employed focus formation and cell proliferation assays, TUNEL staining, cytological analysis, and RT-qPCR to compare the effects of human TAF-Iα and TAF-Iβ genes, transiently expressed in Rat2 cells and in Misgurnus fossilis loaches. We found that both TAF-I isoforms possessed equal oncogenic potential in these systems. Furthermore, an overexpression of human TAF-Iα and TAF-Iβ in Rat2 cells promoted their proliferation. Accordingly, the mitotic index was increased in the transgenic loaches expressing human TAF-Iα or TAF-Iβ. TUNEL assay as well as downregulation of p53 gene and upregulation of bcl-2 gene in these transgenic loaches demonstrated that both isoforms suppressed apoptosis. Thus, TAF-Iα isoform exerts the same oncogenic potential as TAF-Iβ, likely by suppressing the apoptosis and promoting cell proliferation.
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Acknowledgements
This study was performed using equipment of the Center of Common Scientific Equipment of the Institute of Molecular Geneticsof National Research Centre “Kurchatov Institute”.
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This work was supported by the Program for Molecular and Cellular Biology from Presidium of Russian Academy of Sciences (01201356275) and Russian Fundamental Scientific Research Programs (АААА-А19-119022290059-8; АААA-А18-118021590132-9. Theme number: 0445-2019-0030).
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Editor: Tetsuji Okamoto
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Nenasheva, V.V., Makarova, I.V., Stepanenko, E.A. et al. Human TAF-Iα promotes oncogenic transformation via enhancement of cell proliferation and suppression of apoptosis. In Vitro Cell.Dev.Biol.-Animal 57, 531–538 (2021). https://doi.org/10.1007/s11626-021-00572-8
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DOI: https://doi.org/10.1007/s11626-021-00572-8