Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family

Tobias Schilling, Elisa Schulze Schleithoff, Astrid Kairat, Gerry Melino, Wolfgang Stremmel, Moshe Oren, Peter H. Krammer, Martina Müller

Research output: Contribution to journalArticlepeer-review

Abstract

p63 and p73 express two main classes of isoforms: isoforms which contain the transactivation domain (TAp73 and TAp63) executing transcriptional activity and dominant-negative isoforms which are truncated at the NH2-terminus acting as operant inhibitors of TAp73, TAp63 and wild-type p53, and thus possessing oncogenic potential. Like wt p53, TAp63 and TAp73 isoforms transactivate target genes that activate apoptosis signaling pathways. In an attempt to understand how the CD95 gene is regulated by the p53 family, we investigated the contributions of a p53-responsive element (RE) within the first intron of the CD95 gene as well as three elements within the promoter. The intronic element conferred transcriptional activation by p53, TAp63 and TAp73 and cooperated with the p53-REs in the promoter of the CD95 gene. Cooperation between the p53-REs in the promoter and the intronic p53-binding site resulted in maximal transcriptional activation of the CD95 gene by the p53 family.

Original languageEnglish
Pages (from-to)399-404
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume387
Issue number2
DOIs
Publication statusPublished - Sep 18 2009

Keywords

  • Apoptosis
  • Chemosensitivity
  • FAS/CD95/TNFRSF6 gene
  • Hepatocellular carcinoma
  • p53
  • p63
  • p73
  • TNFR superfamily

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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