| Induction of cullin 7 by DNA damage attenuates p53 function. | |
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MedLine Citation:
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PMID: 17586686 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The p53 tumor suppressor gene encodes a transcription factor, which is translationally and posttranslationally activated after DNA damage. In a proteomic screen for p53 interactors, we found that the cullin protein Cul7 efficiently associates with p53. After DNA damage, the level of Cul7 protein increased in a caffeine-sensitive, but p53-independent, manner. Down-regulation of Cul7 by conditional microRNA expression augmented p53-mediated inhibition of cell cycle progression. Ectopic expression of Cul7 inhibited activation of p53 by DNA damaging agents and sensitized cells to adriamycin. Although Cul7 recruited the F-box protein FBX29 to p53, the combined expression of Cul7/FBX29 did not promote ubiquitination and degradation of p53 in vivo. Therefore, the inhibition of p53 activity by Cul7 is presumably mediated by alternative mechanisms. The interplay between p53 and Cul7 resembles the negative feedback loop described for p53 and Mdm2. Pharmacological modulation of Cul7 function may allow the sensitization of cancer cells expressing wild-type p53 to genotoxic agents used in cancer therapy. |
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Authors:
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Peter Jung; Berlinda Verdoodt; Aaron Bailey; John R Yates; Antje Menssen; Heiko Hermeking |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-22 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-04 Completed Date: 2007-09-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 11388-93 Citation Subset: IM |
Affiliation:
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Molecular Oncology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Cullin Proteins / biosynthesis*, genetics*, physiology DNA Damage / physiology* Enzyme Induction / genetics Humans Tumor Suppressor Protein p53 / antagonists & inhibitors*, physiology* |
| Chemical | |
Reg. No./Substance:
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0/CUL7 protein, human; 0/Cullin Proteins; 0/Tumor Suppressor Protein p53 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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