Document Detail

Ultraviolet-B-induced G1 arrest is mediated by downregulation of cyclin-dependent kinase 4 in transformed keratinocytes lacking functional p53.
MedLine Citation:
PMID:  11982759     Owner:  NLM     Status:  MEDLINE    
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.
Arianna L Kim; Mohammad Athar; David R Bickers; Jean Gautier
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  118     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-01     Completed Date:  2002-06-13     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  818-24     Citation Subset:  IM    
Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
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MeSH Terms
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
Keratinocytes / cytology,  enzymology*,  radiation effects
Multienzyme Complexes / antagonists & inhibitors
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
Reg. No./Substance:
0/Multienzyme Complexes; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 136601-57-5/Cyclin D1; EC protein, human; EC Kinase 4; EC Kinases; EC 3.4.22.-/Cysteine Endopeptidases; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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