title: Transcription factor cyclic adenosine monophosphate responsive element binding protein negatively regulates tumor necrosis factor alpha-induced protein 1 expression.
abstract: Tumor necrosis factor alpha (TNFα)-induced protein 1 (TNFAIP1) was originally identified as a protein involved in DNA replication, DNA damage repair, apoptosis and the progression of certain diseases, such as Alzheimer's disease. In the present study, forskolin, a stimulant of cyclic adenosine monophosphate (cAMP), was found to significantly reduce human TNFAIP1 mRNA levels and TNFAIP1 promoter activity in the SKNSH human neuroblastoma cell line as indicated by polymerase chain reaction analysis and a luciferase reporter assay. The association between transcription factor cAMP response element‑binding protein (CREB) and TNFAIP1 was further investigated using loss- and gain of function-studies with western blot analysis and luciferase reporter assays. The CREB-specific inhibitor KG‑501 significantly increased TNFAIP1 protein levels, while overexpression of wild‑type CREB, but not CREB mutated at ser133a or its DNA-binding site, significantly decreased human TNFAIP1 protein levels and TNFAIP1 promoter activity in SKNSH cells. Furthermore, two CRE sites located at ‑285 and ‑425 bp of the human TNFAIP1 promoter were identified to be responsible for CREB‑induced inhibition of human TNFAIP1 promoter activity. Chromatin immunoprecipitation assays confirmed that CREB bound to the TNFAIP1 promoter region harboring these two CRE sites. A further luciferase reporter assay demonstrated that CREB phosphorylation on ser133 was responsible for forskolin‑induced inhibition of TNFAIP1 expression. In conclusion, the present study suggested that CREB is a negative regulator of the TNFAIP1 gene.
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wei
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xun
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Gan
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Guie
authors.initials: G
authors.lastname: Xie
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Molecular Medicine, College of Biology, Hunan University, Changsha, Hunan 410081, P.R. China.
authors.forename: Yinke
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of the Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China.
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D011506:Proteins; D012333:RNA, Messenger; C115968:TNFAIP1 protein, human; D005576:Colforsin