| Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1. | |
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MedLine Citation:
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PMID: 10363976 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Progression of cells through the G1 phase of the cell cycle requires cyclin D:Cdk4/6 and cyclin E:Cdk2 complexes; however, the duration and ordering of these complexes remain unclear. To address this, we synthesized a peptidyl mimetic of the Cdk4/6 inhibitor, p16INK4a that contained an NH2-terminal TAT protein transduction domain. Transduction of TAT-p16 wild-type peptides into cells resulted in the loss of active, hypophosphorylated pRb and elicited an early G1 cell cycle arrest, provided cyclin E:Cdk2 complexes were inactive. We conclude that cyclin D:Cdk4/6 activity is required for early G1 phase cell cycle progression up to, but not beyond, activation of cyclin E:Cdk2 complexes at the restriction point and is thus nonredundant with cyclin E:Cdk2 in late G1. |
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Authors:
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D R Gius; S A Ezhevsky; M Becker-Hapak; H Nagahara; M C Wei; S F Dowdy |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 59 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1999 Jun |
Date Detail:
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Created Date: 1999-06-29 Completed Date: 1999-06-29 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2577-80 Citation Subset: IM |
Affiliation:
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Howard Hughes Medical Institute and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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CDC2-CDC28 Kinases* Cell Line Cyclin D Cyclin E / physiology Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 Cyclin-Dependent Kinase Inhibitor p16 / physiology* Cyclin-Dependent Kinases / physiology* Cyclins / physiology* G1 Phase / physiology* Humans Keratinocytes Phosphorylation Protein-Serine-Threonine Kinases / physiology* Proto-Oncogene Proteins* Retinoblastoma Protein / metabolism* Transfection |
| Grant Support | |
ID/Acronym/Agency:
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CA09547-13/CA/NCI NIH HHS; GM07200/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclin D; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclins; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/CDK6 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 6; EC 2.7.11.22/Cyclin-Dependent Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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