Document Detail

p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2.
MedLine Citation:
PMID:  15827088     Owner:  NLM     Status:  MEDLINE    
The progression of normal cells from G2 into mitosis is stably blocked when their DNA is damaged. Tumor cells lacking p53 arrest only transiently in G2, but eventually enter mitosis. We show that an important component of the stable G2 arrest in normal cells is the transcriptional repression of more than 20 genes encoding proteins needed to enter into and progress through mitosis. Studies from a number of labs including our own have shown that, by inducing p53 and p21/WAF1, DNA damage can trigger RB-family-dependent transcriptional repression. Our studies reported here show that p130 and p107 play a key role in transcriptional repression of genes required for G2 and M in response to DNA damage. For plk1, repression is partially abrogated by loss of p130 and p107, and is completely abrogated by loss of all three RB-family proteins. Mouse cells lacking RB-family proteins do not accumulate with a 4N content of DNA when exposed to adriamycin, suggesting that all three RB-family proteins contribute to G2 arrest in response to DNA damage. Stable arrest in the presence of functional p53-to-RB signaling is probably due to the ability of cells to exit the cell cycle from G2, a conclusion supported by our observation that KI67, a marker of cell-cycle entry, is downregulated in both G1 and G2 in a p53-dependent manner.
Mark W Jackson; Mukesh K Agarwal; Jinbo Yang; Patrick Bruss; Takeshi Uchiumi; Munna L Agarwal; George R Stark; William R Taylor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-04-12
Journal Detail:
Title:  Journal of cell science     Volume:  118     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-29     Completed Date:  2005-09-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1821-32     Citation Subset:  IM    
Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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MeSH Terms
Antibiotics, Antineoplastic / pharmacology
Blotting, Northern
Blotting, Western
Cell Cycle
Cell Cycle Proteins / metabolism
Cell Proliferation
Cell Separation
Cyclin-Dependent Kinase Inhibitor p21
DNA / metabolism
DNA Damage*
Doxorubicin / pharmacology
Flow Cytometry
G2 Phase
Ki-67 Antigen / biosynthesis
Models, Biological
Nuclear Proteins / physiology*
Protein Binding
Proteins / physiology*
Retinoblastoma Protein / physiology*
Retinoblastoma-Like Protein p107
Retinoblastoma-Like Protein p130
Signal Transduction
Time Factors
Transcription, Genetic*
Tumor Suppressor Protein p53 / metabolism
Grant Support
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/CDKN1A protein, human; 0/Cdkn1a protein, mouse; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Ki-67 Antigen; 0/Nuclear Proteins; 0/Proteins; 0/RBL1 protein, human; 0/RBL2 protein, human; 0/Rbl2 protein, mouse; 0/Retinoblastoma Protein; 0/Retinoblastoma-Like Protein p107; 0/Retinoblastoma-Like Protein p130; 0/Tumor Suppressor Protein p53; 23214-92-8/Doxorubicin; 9007-49-2/DNA

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