Inhibition of BETs prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells.

Nan Zhou, Ye Zhang, Gongyun Lei, Yifan Chen, Ting Lin, Qin Liu, Yinshuang Zhao, Jiahui Mao, Yongying Jiang, Renfang Mao

Genes & genomics 2022 Oct

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Heat shock response is a protected mechanism against environmental changes for the organism, which must be tightly regulated. Bromodomain and extra terminal-containing protein family (BETs) regulate numerous gene expression in many physiological and pathological conditions, including viral infection. SV40 is considered as a highly human disease-associated virus. We aimed to explore whether BETs play a role in heat shock in SV40 large T antigen transfected cells. SV40LTA was transfected in HeLa cells using the Lipofectamine 8000. BETs inhibitor JQ1 and I-BET-762 was employed to treat transfected cells and HEK-293 T cells. Heat shock treatment was performed to determine the effect of JQ1 and I-BET-762 on these cells. Western blot and quantitative RT-PCR were carried out to assess the expression of HSP70 and other HSPs. We found that inhibition of BETs by JQ1 and I-BET-762 protects cells from heat shock-induced death in HEK293T cells. Both JQ1 and I-BET-762 induce the expression of HSPs and HSF1 in HEK-293 T cells. However, neither JQ1 nor I-BET-762 fail to induce the expression of HSPs in either HeLa or HBL-1 cells. When SV40 large T antigen was transfected into HeLa cells, the induction of HSP70 expressing and the protection of heat shock-induced cell death are reproduced by JQ1 and IBET treatment in these transfected cells. Inhibition of BETs by JQ1 and I-BET-762 prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells. Our data indicate a novel function of BETs in SV40 large T antigen transformed cells, affecting HSPs and HSF1 as well as its function on heat shock response. © 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.

Citation

Nan Zhou, Ye Zhang, Gongyun Lei, Yifan Chen, Ting Lin, Qin Liu, Yinshuang Zhao, Jiahui Mao, Yongying Jiang, Renfang Mao. Inhibition of BETs prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells. Genes & genomics. 2022 Oct;44(10):1259-1269