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BTG2/PC3/Tis21 decreases Bcl-xL mRNA stability in cancer cells

Choi, YongWon; Lim, InKyoung
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine
BTG2/PC3/Tis21, as one of the human BTG/TOB protein family members, comprises six members (BTG1, BTG2, BTG3, BTG4, TOB1 and TOB2) that are characterised by a conserved BTG domain containing box A and box B. This conserved BTG domain mediates its interactions with the Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not mRNA deadenylase complex. In addition, BTG domain containing box C in Btg1 and Btg2 interacts with Protein Arginine Methyltransferase (PRMT1), which regulates RNA binding proteins. Thus, BTG2 can regulate mRNA stability through its interaction with Caf1 and PRMT1. However, it is still unclear whether BTG2 is involved in general or specific mRNA decay. Here we screened the mRNAs degradation rate of several genes in BTG2-overexpressed cells, compared to control cells. Interestingly, the mRNA stability of Bcl-xL was decreased in BTG2-overexpressed cancer cells. Furthermore, these BTG2-overexpressed cells were more sensitive to apoptosis, induced by actinomycin D, UV irradiation. Thus, the aim of this study is to investigate the mechanism of how BTG2 regulates the mRNA stability of Bcl-xL and what its biological significance is.
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