Transcription factor cyclic adenosine monophosphate responsive element binding protein negatively regulates tumor necrosis factor alpha-induced protein 1 expression

  • Authors:
    • Ning Liu
    • Ke Wei
    • Yu Xun
    • Xiaoxu Yang
    • Shiquan Gan
    • Hui Xiao
    • Ye Xiao
    • Feng Yan
    • Guie Xie
    • Tingting Wang
    • Yinke Yang
    • Jian Zhang
    • Xiang Hu
    • Shuanglin Xiang
  • View Affiliations

  • Published online on: September 17, 2015     https://doi.org/10.3892/mmr.2015.4336
  • Pages: 7763-7769
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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.
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November-2015
Volume 12 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Liu N, Wei K, Xun Y, Yang X, Gan S, Xiao H, Xiao Y, Yan F, Xie G, Wang T, Wang T, et al: Transcription factor cyclic adenosine monophosphate responsive element binding protein negatively regulates tumor necrosis factor alpha-induced protein 1 expression. Mol Med Rep 12: 7763-7769, 2015
APA
Liu, N., Wei, K., Xun, Y., Yang, X., Gan, S., Xiao, H. ... Xiang, S. (2015). Transcription factor cyclic adenosine monophosphate responsive element binding protein negatively regulates tumor necrosis factor alpha-induced protein 1 expression. Molecular Medicine Reports, 12, 7763-7769. https://doi.org/10.3892/mmr.2015.4336
MLA
Liu, N., Wei, K., Xun, Y., Yang, X., Gan, S., Xiao, H., Xiao, Y., Yan, F., Xie, G., Wang, T., Yang, Y., Zhang, J., Hu, X., Xiang, S."Transcription factor cyclic adenosine monophosphate responsive element binding protein negatively regulates tumor necrosis factor alpha-induced protein 1 expression". Molecular Medicine Reports 12.5 (2015): 7763-7769.
Chicago
Liu, N., Wei, K., Xun, Y., Yang, X., Gan, S., Xiao, H., Xiao, Y., Yan, F., Xie, G., Wang, T., Yang, Y., Zhang, J., Hu, X., Xiang, S."Transcription factor cyclic adenosine monophosphate responsive element binding protein negatively regulates tumor necrosis factor alpha-induced protein 1 expression". Molecular Medicine Reports 12, no. 5 (2015): 7763-7769. https://doi.org/10.3892/mmr.2015.4336