The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73

A. Peschiaroli, F. Scialpi, F. Bernassola, M. Pagano, G. Melino

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription factor p73, a member of the p53 family, mediates cell-cycle arrest and apoptosis in response to DNA damage-induced cellular stress, acting thus as a proapoptotic gene. Similar to p53, p73 activity is regulated by post-translational modification, including phosphorylation, acetylation and ubiquitylation. In C. elegans, the F-box protein FSN-1 controls germline apoptosis by regulating CEP-1, the single ancestral p53 family member. Here we report that FBXO45, the human ortholog of FSN-1, binds specifically to p73 triggering its proteasome-dependent degradation. Importantly, SCF FBXO45 ubiquitylates p73 both in vivo and in vitro. Moreover, siRNA-mediated depletion of FBXO45 stabilizes p73 and concomitantly induces cell death in a p53-independent manner. All together, these results show that the orphan F-box protein FBXO45 regulates the stability of p73, highlighting a conserved pathway evolved from nematode to human by which the p53 members are regulated by an SCF-dependent mechanism.

Original languageEnglish
Pages (from-to)3157-3166
Number of pages10
JournalOncogene
Volume28
Issue number35
DOIs
Publication statusPublished - Sep 3 2009

Keywords

  • Degradation
  • F-box proteins
  • P73
  • Proteasome
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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