Identification of a functional p53 responsive element within the promoter of XAF1 gene in gastrointestinal cancer cells

  • Authors: Wenjing Zhang, Zheng Guo, Bo Jiang, Lingyun Niu, Guosheng Xia, Xinying Wang, Tianming Cheng, Yusheng Zhang, Jide Wang
  • View Affiliations

  • Published online on: Thursday, April 1, 2010
  • Pages: 1031-1037
  • DOI: 10.3892/ijo_00000584

Abstract

It has been reported that XAF1 expression in gastric cancer is negatively correlated with p53. Our purpose was to clarify the regulatory mechanism of p53 on XAF1 expression. The effects of overexpressed wild-type and mutant p53 on XAF1 expression were evaluated. Binding capacity of core XAF1 promoter sequence to the recombinant p53 protein was examined. Site-directed mutation of putative p53 binding sequence and p53 knockdown by siRNA were performed. The protein expression and promoter activities of XAF1 in cells with null p53 were higher than that with wild-type and mutant p53. Ectopic overexpression of wild-type p53 suppressed XAF1 expression. A half-site (−95 to −86 nt) and a quarter-site (−4 to +1 nt) of p53 responsive element were found within XAF1 promoter. Both sequences bound to recombinant p53 effectively and specifically. Site-mutation of p53 responsive sequences abrogated the binding capacity. However, only the mutation of half-site increased XAF1 promoter activities. Suppression of p53 not only decreased the binding capacity of p53 responsive halfsite but also increased XAF1 transcription. In conclusion, we demonstrated that p53 could suppress the transcription of XAF1 through interaction with a high affinity responsive element (−95 to −86 nt) within XAF1 promoter, indicating a novel exclusive mechanism between these two tumor suppressors.
Journal Cover

April 2010
Volume 36 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Zhang, W., Guo, Z., Jiang, B., Niu, L., Xia, G., Wang, X., Cheng, T., Zhang, Y., & Wang, J. (2010). Identification of a functional p53 responsive element within the promoter of XAF1 gene in gastrointestinal cancer cells. International Journal of Oncology, 36(4), 1031-1037.
MLA
Zhang, Guo, Jiang, Niu, Xia, Wang, Cheng, Zhang, and Jide Wang. "Identification of a functional p53 responsive element within the promoter of XAF1 gene in gastrointestinal cancer cells." International Journal of Oncology International Journal of Oncology 36.4 (2010): 1031-1037.
Chicago
Zhang, Guo, Jiang, Niu, Xia, Wang, Cheng, Zhang, and Jide Wang. "Identification of a functional p53 responsive element within the promoter of XAF1 gene in gastrointestinal cancer cells." International Journal of Oncology International Journal of Oncology 36 no. 4 (2010): 1031-1037.