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.

The Ubiquitin-Protein Ligase Itch regulates p73 stability

DE LAURENZI, Vincenzo;
2005-01-01

Abstract

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.
File in questo prodotto:
File Dimensione Formato  
Rossi-etal.pdf

Solo gestori archivio

Tipologia: PDF editoriale
Dimensione 772.64 kB
Formato Adobe PDF
772.64 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/133053
Citazioni
  • ???jsp.display-item.citation.pmc??? 128
  • Scopus 276
  • ???jsp.display-item.citation.isi??? 268
social impact