- 作者: Zi-Miao Liu; Huei-Sheng Huang
- 中文摘要: --
- 英文摘要: 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 Spl 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/ HDACl to the Spl sites and then represses p21 expression. That is, TGIF is involved in As2O3-Inhibited p21 expression, and then blocks the cell cycle arrest.
- 中文關鍵字: --
- 英文關鍵字: As2O3 ?p21WAF1/CIP1 ?TGIF ?c-Jun ?HDAC1