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Inhibitory role of TGIF in the As2O3-regulated p21WAF1/CIP1 expression

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Although arsenic is an infamous carcinogen, it has been effectively used to treat acute promyelocytic leukemia, and can induce cell cycle arrest or apoptosis in human solid tumors. Previously, we had demonstrated that opposing effects of ERK1/2 and JNK on p21 expression in response to arsenic trioxide (As2O3) are mediated through the Sp1 responsive elements of the p21 promoter in A431 cells. Presently, we demonstrate that Sp1, and c-Jun functionally cooperate to activate p21 promoter expression through Sp1 binding sites (−84/−64) by using DNA affinity binding, chromatin immunoprecipitation, and promoter assays. Surprisingly, As2O3-induced c-Jun(Ser63/73) phosphorylation can recruit TGIF/HDAC1 to the Sp1 binding sites and then suppress p21 promoter activation. We suggest that, after As2O3 treatment, the N-terminal domain of c-Jun phosphorylation by JNK recruits TGIF/HDAC1 to the Sp1 sites and then represses p21 expression. That is, TGIF is involved in As2O3-inhibited p21 expression, and then blocks the cell cycle arrest.

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Acknowledgements

We are greatly indebted to Dr. Wen-Chang Chang for his valuable discussions. This work was supported by grant NSC95-2320-B-006-055-MY3 from National Science Council of Taiwan.

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Authors and Affiliations

  1. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan

    Zi-Miao Liu & Huei-Sheng Huang

  2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan

    Zi-Miao Liu

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  1. Zi-Miao Liu
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Correspondence to Huei-Sheng Huang.

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Liu, ZM., Huang, HS. Inhibitory role of TGIF in the As2O3-regulated p21WAF1/CIP1 expression. J Biomed Sci 15, 333–342 (2008). https://doi.org/10.1007/s11373-007-9232-9

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  • DOI: https://doi.org/10.1007/s11373-007-9232-9

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