Human TAF-Iα promotes oncogenic transformation via enhancement of cell proliferation and suppression of apoptosis

In Vitro Cell Dev Biol Anim. 2021 May;57(5):531-538. doi: 10.1007/s11626-021-00572-8. Epub 2021 May 21.

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.

Keywords: Apoptosis; Misgurnus fossilis; Oncogenesis; Rat2 cells; TAF-Iα; TAF-Iβ.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis*
  • Cell Proliferation*
  • Cell Transformation, Neoplastic / metabolism*
  • Cypriniformes
  • DNA-Binding Proteins / physiology*
  • Fibroblasts / metabolism
  • Histone Chaperones / physiology*
  • Humans
  • Mitosis
  • Real-Time Polymerase Chain Reaction

Substances

  • DNA-Binding Proteins
  • Histone Chaperones
  • SET protein, human