p73 induces apoptosis by different mechanisms

Saafa Ramadan, Alessandro Terrinoni, Maria Valeria Catani, A. Emre Sayan, Richard A. Knight, Martina Mueller, Peter H. Krammer, Gerry Melino, Eleonora Candi

Research output: Contribution to journalArticlepeer-review

Abstract

p73, like its homologue, the tumor suppressor p53, is able to induce apoptosis in several cell types. This property is important for the involvement of p73 in cancer development and therapy. However, in contrast with p53, the TAp73 gene has two distinct promoters coding for two protein isoforms with opposite effects: while the transactivation proficient TAp73 shows pro-apoptotic effects, the amino-terminal-deleted ΔNp73 has an anti-apoptotic function. Indeed, the relative expression of these two proteins is related to the prognosis of several cancers. Here we discuss recent developments in the control of p73-induced apoptosis. First, TAp73 induces ER stress via the direct transactivation of Scotin. Second, TAp73 induces the mitochondrial pathway by directly transactivating both Bax and the BH3 only protein PUMA promoters. While the first transactivation is weak, and not sufficient to trigger apoptosis (at least in the in vitro cellular models so far evaluated), the induction of PUMA is strong and lethal. Third, the promoter of the death receptor CD95 contains a p53 responsive element and preliminary experiments suggest that TAp73 also activates the death receptor pathway. In addition, TAp73 is able to transactivate its own second promoter, thus inducing the expression of the anti-apoptotic ΔNp73 isoform. Therefore, the balance between TAp73 and ΔNp73 finely regulates cellular sensitivity to death.

Original languageEnglish
Pages (from-to)713-717
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume331
Issue number3
DOIs
Publication statusPublished - Jun 10 2005

Keywords

  • Apoptosis
  • Bax
  • Cancer
  • CD95
  • Cell death
  • Death receptor
  • DNA damage
  • p53
  • p63
  • p73
  • PUMA
  • Scotin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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