Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Cul7 is a member of the Cullin Ring Ligase (CRL) family and is required for normal mouse development and cellular proliferation. Recently, a region of Cul7 that is highly conserved in the p53-associated, Parkin-like cytoplasmic protein PARC, was shown to bind p53 directly. Here we identify the CPH domains (conserved domain within Cul7, PARC, and HERC2 proteins) of both Cul7 and PARC as p53 interaction domains using size exclusion chromatography and NMR spectroscopy. We present the first structure of the evolutionarily conserved CPH domain and provide novel insight into the Cul7-p53 interaction. The NMR structure of the Cul7-CPH domain reveals a fold similar to peptide interaction modules such as the SH3, Tudor, and KOW domains. The p53 interaction surface of both Cul7 and PARC CPH domains was mapped to a conserved surface distinct from the analogous peptide-binding regions of SH3, KOW, and Tudor domains, suggesting a novel mode of interaction. The CPH domain interaction surface of p53 resides in the tetramerization domain and is formed by residues contributed by at least two subunits.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M611297200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization.
J Biol Chem
May 2014
From the Departament de Ciències Fisiològiques II, Campus de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona 08907, Spain
The tumor suppressor p53 is a transcription factor that coordinates the cellular response to several kinds of stress. p53 inactivation is an important step in tumor progression. Oligomerization of p53 is critical for its posttranslational modification and its ability to regulate the transcription of target genes necessary to inhibit tumor growth.
View Article and Find Full Text PDFThe cullin protein family.
Genome Biol
February 2012
Institute of Pharmacology and Toxicology, Technische Universität München, 80802 Munich, Germany.
Cullin proteins are molecular scaffolds that have crucial roles in the post-translational modification of cellular proteins involving ubiquitin. The mammalian cullin protein family comprises eight members (CUL1 to CUL7 and PARC), which are characterized by a cullin homology domain. CUL1 to CUL7 assemble multi-subunit Cullin-RING E3 ubiquitin ligase (CRL) complexes, the largest family of E3 ligases with more than 200 members.
View Article and Find Full Text PDFDiversification of the cullin family.
BMC Evol Biol
November 2009
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, Valencia, Spain.
Background: Cullins are proteins involved in ubiquitination through their participation in multisubunit ubiquitin ligase complexes. In this study, I use comparative genomic data to establish the pattern of emergence and diversification of cullins in eukaryotes.
Results: The available data indicate that there were three cullin genes before the unikont/bikont split, which I have called Culalpha, Culbeta and Culgamma.
PARC and CUL7 form atypical cullin RING ligase complexes.
Cancer Res
March 2007
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
CUL7 and the p53-associated, PARkin-like cytoplasmic protein (PARC) were previously reported to form homodimers and heterodimers, the first demonstration of cullin dimerization. Although a CUL7-based SKP1/CUL1/F-box (SCF)-like complex has been observed, little is known about the existence of a PARC-based SCF-like complex and how PARC interacts with CUL7-based complexes. To further characterize PARC-containing complexes, we examined the ability of PARC to form an SCF-like complex.
View Article and Find Full Text PDFThe conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53.
J Biol Chem
April 2007
Ontario Cancer Institute and the Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Cul7 is a member of the Cullin Ring Ligase (CRL) family and is required for normal mouse development and cellular proliferation. Recently, a region of Cul7 that is highly conserved in the p53-associated, Parkin-like cytoplasmic protein PARC, was shown to bind p53 directly. Here we identify the CPH domains (conserved domain within Cul7, PARC, and HERC2 proteins) of both Cul7 and PARC as p53 interaction domains using size exclusion chromatography and NMR spectroscopy.
View Article and Find Full Text PDF