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KMID : 0381120220440101259
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Genes and Genomics
2022 Volume.44 No. 10 p.1259 ~ p.1269
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Inhibition of BETs prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells
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Zhou Nan
Zhang Ye
Lei Gongyun
Chen Yifan
Lin Ting
Liu Qin
Zhao Yinshuang
Mao Jiahui
Jiang Yongying
Mao Renfang
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Abstract
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Background: 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.
Objective: We aimed to explore whether BETs play a role in heat shock in SV40 large T antigen transfected cells.
Methods: 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.
Results: 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.
Conclusions: 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.
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KEYWORD
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Heat shock response, BETs inhibitor, HSPs, SV40 large T antigen
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