| Ultraviolet-B-induced G1 arrest is mediated by downregulation of cyclin-dependent kinase 4 in transformed keratinocytes lacking functional p53. | |
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MedLine Citation:
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PMID: 11982759 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In order to identify potential novel targets for ultraviolet-B-induced skin tumorigenesis, we assessed the effect of ultraviolet-B exposure on cell cycle progression of transformed keratinocytes with mutant p53. We show that ultraviolet-B exposure of human epidermoid carcinoma A431 cells results in G1 cell cycle arrest in both asynchronously growing and synchronized cells. A significant increase in G1 cell population was observed following exposure to doses of ultraviolet-B as low as 10 mJ per cm2. When irradiated with ultraviolet-B, cells synchronized in G1 with mimosine did not exit G1. G1 cell cycle arrest was associated with a decrease in the hyperphosphorylated forms of retinoblastoma protein that was detectable within 4 h and gradually disappeared by 12 h. We also observed a decrease in cyclins D1, D2, and D3, and cyclin-dependent kinase 4 proteins, and a concomitant decrease in cyclin-dependent kinase 4/cyclin D1 associated kinase activity, whereas ultraviolet-B exposure had no effect on cyclin-dependent kinase 2 and cyclin-dependent kinase 6 levels during this time period. Incubation of cells with proteasome inhibitors MG-115 and MG-132 prevented the decrease in cyclin D1, D2, and D3, and cyclin-dependent kinase 4 protein. Taken together, our results suggest that ultraviolet-B-induced cell cycle arrest in A431 cells is mediated by cyclin-dependent kinase 4 downregulation. This identifies a novel pathway for G1 cell cycle arrest in transformed keratinocytes following ultraviolet-B irradiation. |
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Authors:
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Arianna L Kim; Mohammad Athar; David R Bickers; Jean Gautier |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 118 ISSN: 0022-202X ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2002 May |
Date Detail:
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Created Date: 2002-05-01 Completed Date: 2002-06-13 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 818-24 Citation Subset: IM |
Affiliation:
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Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Carcinoma, Squamous Cell Cell Line, Transformed Cyclin D1 / genetics, metabolism Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases / genetics, metabolism* Cysteine Endopeptidases Down-Regulation / radiation effects G1 Phase / radiation effects* Gene Expression Regulation, Enzymologic / radiation effects Humans Keratinocytes / cytology, enzymology*, radiation effects Multienzyme Complexes / antagonists & inhibitors Phosphorylation Proteasome Endopeptidase Complex Proto-Oncogene Proteins* RNA, Messenger / analysis Retinoblastoma Protein / metabolism Skin Neoplasms Tumor Cells, Cultured Tumor Suppressor Protein p53 / genetics* Ultraviolet Rays |
| Grant Support | |
ID/Acronym/Agency:
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R01 ES01900-22/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Multienzyme Complexes; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 136601-57-5/Cyclin D1; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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