Transcriptional upregulation of DNA polymerase beta by TEIF.
The overexpression of DNA polymerase beta (beta-pol) has been identified in lots of human cancers, but the mechanism has seldom been investigated. Telomerase transcriptional element-interacting factor (TEIF) can bind to hTERT promoter, stimulating its transcription and telomerase activities. Here, we report that TEIF could also enhance the expression of beta-pol at transcription level. TEIF could specifically activate transcription of beta-pol promoter, but not that of DNA polymerase alpha or delta promoter. The responsible sequences for binding of TEIF were revealed as GC-rich elements dispersing from +19 to -29 nt of beta-pol promoter, which due to mutations caused decreasing in binding of TEIF and apparent losing of transactivation activity. The in vivo interaction between TEIF and beta-pol promoter was identified by chromatin immunoprecipitation assay. Besides, ectopic expression of TEIF in HeLa cells could upregulate both levels of endogenous beta-pol mRNA and protein, and consequently increases resistance to the oxidative stress of H2O2. The data may provide new clue to the elucidation of beta-pol overexpression in cancers and also a functional link between beta-pol and telomerase.
Zhao
Yuanjun
Y
Department of Pathology, Health Science Center, Peking University, Beijing 100083, China.
Zheng
Jie
J
Ling
Yun
Y
Hou
Lin
L
Zhang
Bo
B
D033942:Adaptor Proteins, Vesicular Transport; D019951:DNA Polymerase beta / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; C464929:SCYL1 protein, human; D014157:Transcription Factors; D019951:DNA Polymerase beta