1. Human TAF-Iα promotes oncogenic transformation via enhancement of cell proliferation and suppression of apoptosis
- Author
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Valentina V, Nenasheva, Irina V, Makarova, Ekaterina A, Stepanenko, Stanislav A, Antonov, Ekaterina V, Novosadova, Anastasia R, Narsullaeva, Larisa V, Kozikova, Ekaterina A, Polteva, Lyudmila A, Sleptsova, Natalya A, Shcherbatova, Nella V, Khaidarova, Lyudmila E, Andreeva, and Vyacheslav Z, Tarantul
- Subjects
Animals, Genetically Modified ,DNA-Binding Proteins ,Cypriniformes ,Cell Transformation, Neoplastic ,Animals ,Humans ,Mitosis ,Apoptosis ,Histone Chaperones ,Fibroblasts ,Real-Time Polymerase Chain Reaction ,Cell Proliferation - 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.
- Published
- 2020