The ubiquitin-protein ligase Itch regulates p73 stability

Mario Rossi, Vincenzo De Laurenzi, Eliana Munarriz, Douglas R. Green, Yun Cai Liu, Karen H. Vousden, Gianni Cesareni, Gerry Melino

Research output: Contribution to journalArticlepeer-review


p73, a member of the p53 family of transcription factors, is upregulated in response to DNA damage, inducing cell cycle arrest and apoptosis. Besides indications that this p73 response is post-transcriptional, little is known about the underlying molecular mechanisms of p73 protein degradation. Ubiquitination and proteasomal-dependent degradation of p53 are regulated by its transcriptional target MDM2. However, unlike p53, p73 binds to, but is not degraded by, MDM2. Here we describe the binding of p73 to Itch, a Hect ubiquitin-protein ligase. Itch selectively binds and ubiquitinates p73 but not p53; this results in the rapid proteasome-dependent degradation of p73. Upon DNA damage Itch itself is downregulated, allowing p73 protein levels to rise and thus interfere with p73 function. In conclusion, we have identified a key mechanism in the control of p73 protein levels both in normal as well as in stress conditions.

Original languageEnglish
Pages (from-to)836-848
Number of pages13
JournalEMBO Journal
Issue number4
Publication statusPublished - Feb 23 2005


  • Degradation
  • E3 ligase
  • p53
  • Proteasome

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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