Regulation of the p73 protein stability and degradation

Andrew Oberst, Mario Rossi, Paolo Salomoni, Pier Paolo Pandolfi, Moshe Oren, Gerry Melino, Francesca Bernassola

Research output: Contribution to journalArticlepeer-review

Abstract

p73, a homologue to the tumor suppressor gene p53, is involved in tumorigenesis, though its specific role remains unclear. The gene has two distinct promoters which allow the formation of two protein isoforms with opposite effects: full-length transactivating (TA) p73 shows pro-apoptotic effects, while the shorter ΔNp73, which lacks the N-terminal transactivating domain, has an evident anti-apoptotic function. Unlike p53, the p73 gene is rarely mutated in human cancers. However, alterations in the relative levels of TA and ΔNp73 have been shown to correlate with prognosis in several human cancers, suggesting that the fine regulation of these two isoforms is of pivotal importance in controlling proliferation and cell death. Much effort is currently focused on the elucidation of the mechanisms that differentially control TA and ΔNp73 activity and protein stability, a process complicated by the finding that both proteins are regulated by a similar suite of complex post-translational modifications that include ubiquitination, sequential phosphorylation, prolyl-isomerization, recruitment into the PML-nuclear body (PML-NB), and acetylation. Here we shall consider the main regulatory partners of p73, with particular attention to the recently discovered Itch- and Nedd8-mediated degradation pathways, along with the emerging roles of PML, p38 MAP kinase, Pin1, and p300 in p73 transcriptional activation, and possible mechanisms for the differential regulation of the TAp73 and ΔNp73 isoforms.

Original languageEnglish
Pages (from-to)707-712
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume331
Issue number3
DOIs
Publication statusPublished - Jun 10 2005

Keywords

  • Apoptosis
  • Cell cycle
  • Cell death
  • DNA damage
  • Itch
  • Nedd8
  • p53
  • p73
  • Protein stability
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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