Identification of human guanylate-binding protein 1 gene (hGBP1) as a direct transcriptional target gene of p53

Biochem Biophys Res Commun. 2013 Jun 28;436(2):204-11. doi: 10.1016/j.bbrc.2013.05.074. Epub 2013 May 29.

Abstract

Human guanylate-binding protein 1 (hGBP1) plays an important role in antitumor and antiviral immune responses. Here, we show that tumor suppressor p53 positively regulated hGBP1 transcription via binding to the p53 response element (p53RE) present in the hGBP1 promoter region. p53 activation by 5-fluorouracil significantly increased hGBP1 expression in wild-type p53 cells, but not in p53-null cells. Knockdown of p53 expression remarkably impaired hGBP1 expression induced by 5-fluorouracil, type I interferon treatment, or influenza A virus infection. Among three deductive p53REs present in the hGBP1 promoter region, two p53REs were found to be transactivated by p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Binding Sites / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Fluorouracil / pharmacology
  • GTP-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • Interferon Type I / pharmacology
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA Interference
  • Response Elements / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*
  • Transcriptional Activation / drug effects
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antimetabolites, Antineoplastic
  • GBP1 protein, human
  • Interferon Type I
  • Tumor Suppressor Protein p53
  • GTP-Binding Proteins
  • Fluorouracil