ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells.
ATF5 transcription factor plays an essential role in hematopoietic and glioma cell survival and neuronal cell differentiation. Here, we report for the first time the pro-apoptosis role of ATF5 and identify Cyclin D3 as an ATF5-targeted apoptosis-related gene. The ectopic expression of ATF5 in HeLa cells could markedly increase cisplatin-induced apoptosis and the cleavage of Caspase-3, and induce Cyclin D3 mRNA expression via cooperation with E2F1 transcription factor. Moreover, the interference of Cyclin D3 expression by transfection with Cyclin D3 RNAi could protect cells from ATF5-mediated apoptosis induced by cisplatin, indicating the contribution of Cyclin D3 in ATF5-mediated apoptosis. Taken together, these results suggest that ATF5 increases cisplatin-induced apoptosis through up-regulation of Cyclin D3 transcription, which elicits survival signals in HeLa cells.
Wei
Yuanyan
Y
State Key Laboratory of Genetic Engineering and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, People's Republic of China.
Jiang
Jianhai
J
Sun
Maoyun
M
Chen
Xiaoning
X
Wang
Hanzhou
H
Gu
Jianxin
J
D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
C507532:ATF5 protein, human; D051696:Activating Transcription Factors; C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D002945:Cisplatin