论文部分内容阅读
TNFAIP1 was originally identified as a tumor necrosis factor alpha(TNFα)-induced protein involvesd in DNA replication,DNA damage repair,cell apoptosis,and some disease progression such as Alzheimers disease.In the present study,forskolin,astimulus of cAMP,was found to significantly reduce human TNFAIP1 mRNA levels and the promoter activity.The relationship between transcription factor CREB(cAMP response element-binding protein)and TNFAIP1 was further investigated.The CREB specific inhibitor KG-501 significantly increased TNFAIP1 protein level; on the other hand,over-expression of wild-type CREB,but not mutated CREB(CREBs133a and KCREB)significantly decreased human TNFAIP1 protein level and TNFAIP1 promoter activity.Moreover,two cAMP response element(CRE)sites located at-50 and-196 of the human TNFAIP1 promoter were identified to be responsible for CREB-mediated inhibition of human TNFAIP1 promoter activity.Chromatin immunoprecipitation(ChIP)assays confirmed that CREB bound to the TNFAIP1 promoter region harboring both CRE sites.In addition,CREB phosphorylation on Ser133 is responsible for forskolin-decreased TNFAIP1 expression.In conclusion,our results suggested that CREB is a negative regulator of the TNFAIP1 gene.