Oncogene, 2013-09, Vol.32 (39), p.4721-4726
2013
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Details
- Autor(en) / Beteiligte
- Titel
- The Cul4A-DDB1 E3 ubiquitin ligase complex represses p73 transcriptional activity
- Ist Teil von
- Oncogene, 2013-09, Vol.32 (39), p.4721-4726
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/onc.2012.463Titel-ID: cdi_proquest_miscellaneous_1443379256
- Format
- –
- Schlagworte
- Animals, Apoptosis, Breast, Breast cancer, Breast carcinoma, Breast Neoplasms - metabolism, Carcinogenesis, Carcinoma - metabolism, Carrier Proteins - physiology, Cell cycle, Cell Line, Cellular control mechanisms, Cullin Proteins - physiology, Deoxyribonucleic acid, DNA, DNA damage, DNA-binding protein, DNA-Binding Proteins - antagonists & inhibitors, DNA-Binding Proteins - metabolism, DNA-Binding Proteins - physiology, Female, Gene expression, Gene Expression Regulation, Neoplastic - physiology, Gene silencing, Genetic aspects, Genetic transcription, HEK293 Cells, Humans, Ligases, Mice, Multiprotein Complexes, Neoplasm Proteins - antagonists & inhibitors, Neoplasm Proteins - physiology, Nuclear Proteins - antagonists & inhibitors, Nuclear Proteins - metabolism, Observations, p53 Protein, p73 Protein, Properties, Protein Binding, Protein Processing, Post-Translational, Protein Stability, Proteins, Proteolysis, RNA-mediated interference, Transcription, Transcription, Genetic - physiology, Tumor Protein p73, Tumor Suppressor Protein p53 - deficiency, Tumor Suppressor Protein p53 - physiology, Tumor Suppressor Proteins - antagonists & inhibitors, Tumor Suppressor Proteins - metabolism, Ubiquitin, Ubiquitin-protein ligase, Ubiquitination