The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity (Articolo in rivista)

Type
Label
  • The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/onc.2012.463 (literal)
Alternative label
  • M. Malatesta 1-10; A. Peschiaroli 2-3; E.M. Memmi 1; J. Zhang 4; A. Antonov 5; D.R. Green 6; N.A. Barlev 7-8; A. V. Garabadgiu 7; P. Zhou 4; G. Melino 1-5-7; F. Bernassola 1-9 (2013)
    The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity
    in Oncogene (Basingstoke)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • M. Malatesta 1-10; A. Peschiaroli 2-3; E.M. Memmi 1; J. Zhang 4; A. Antonov 5; D.R. Green 6; N.A. Barlev 7-8; A. V. Garabadgiu 7; P. Zhou 4; G. Melino 1-5-7; F. Bernassola 1-9 (literal)
Pagina inizio
  • 4721 (literal)
Pagina fine
  • 4726 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • Oncogene advance online publication, 22 October 2012. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 32 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 39 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy. 2 IDI-IRCCS, Biochemistry Laboratory, Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy. 3 Department of Biomedicine, Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy. 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and Weill Cornell Graduate School of Medical Sciences, New York, NY, USA. 5 Medical Research Council, Toxicology Unit, University of Leicester, Leicester, UK. 6 Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA. 7 Saint-Petersburg State Institute of Technology, Saint-Petersburg, Russia. 8 Department of Biochemistry, University of Leicester, Leicester, UK. 9 Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. (literal)
Titolo
  • The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity (literal)
Abstract
  • The Cullin4A (cul4A)-dependent ligase (CDL4A) E3 has been implicated in a variety of biological processes, including cell cycle progression and DNA damage response. Remarkably, CDL4A exerts its function through both proteolytic and non-proteolytic events. Here, we show that the p53 family member p73 is able to interact with the CDL4A complex through its direct binding to the receptor subunit DNA-binding protein 1 (DDB1). As a result, the CDL4A complex is able to monoubiquitylate p73. Modification of p73 by CDL4A-mediated ubiquitylation does not affect p73 protein stability, but negatively regulates p73-dependent transcriptional activity. Indeed, genetic or RNA interference-mediated depletion of DDB1 induces the expression of several p73 target genes in a p53-independent manner. In addition, by exploiting a bioinformatic approach, we found that elevated expression of Cul4A in human breast carcinomas is associated with repression of p73 target genes. In conclusion, our findings add a novel insight into the regulation of p73 by the CDL4A complex, through the inhibition of its transcriptional function. (literal)
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