| Reciprocal regulation via protein-protein interaction between c-Myc and p21(cip1/waf1/sdi1) in DNA replication and transcription. | |
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MedLine Citation:
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PMID: 10744738 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The c-myc protooncogene product (c-Myc) is a transcription factor and is rapidly induced in resting cells following various mitogenic stimuli. c-Myc is thus suggested to play an important role in the transition from quiescence to proliferation. Despite numerous studies, including those on the connection between cyclin E/cyclin-dependent kinase 2 and c-Myc, little has been clarified about c-Myc in terms of the cell cycle regulation. Here we show that c-Myc can directly bind to the carboxyl-terminal region of the cyclin-dependent kinase inhibitor p21(cip1/waf1/sdi1) and thus partially relieves the p21 of the inhibitory effect on DNA synthesis directed by the proliferating cell nuclear antigen-dependent DNA polymerase delta. As for transcription, on the other hand, the p21 binding to the Myc box II region of c-Myc blocks c-Myc-Max complex formation on the E-box and thereby suppresses the transcriptional activation from the E-box by c-Myc. These results suggest that c-Myc activates DNA replication via inactivation of p21 and that p21, vice versa, represses the transcriptional activity of c-Myc. The balance of the reciprocal inactivation between c-Myc and p21 may determine the course of cellular processes such as cell proliferation, differentiation, and apoptosis. |
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Authors:
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H Kitaura; M Shinshi; Y Uchikoshi; T Ono; S M Iguchi-Ariga; H Ariga |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 275 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-08 Completed Date: 2000-05-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 10477-83 Citation Subset: IM |
Affiliation:
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Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Binding, Competitive Cloning, Molecular Cyclin-Dependent Kinase Inhibitor p21 Cyclins / isolation & purification, metabolism* DNA Replication* Enzyme Inhibitors / metabolism Escherichia coli Genes, myc Proliferating Cell Nuclear Antigen / metabolism Proto-Oncogene Proteins c-myc / chemistry, isolation & purification, metabolism* Recombinant Fusion Proteins / metabolism Recombinant Proteins / chemistry, isolation & purification, metabolism Transcription, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/Proliferating Cell Nuclear Antigen; 0/Proto-Oncogene Proteins c-myc; 0/Recombinant Fusion Proteins; 0/Recombinant Proteins |
| Comments/Corrections | |
Erratum In:
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J Biol Chem 2000 May 26;275(21):16400 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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