CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gjerset, R. A.
Right arrow Articles by Mercola, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gjerset, R. A.
Right arrow Articles by Mercola, D.
Cell Growth & Differentiation Vol. 10, 545-554, August 1999
© 1999 American Association for Cancer Research

Inhibition of the Jun Kinase Pathway Blocks DNA Repair, Enhances p53-mediated Apoptosis and Promotes Gene Amplification1

Ruth A. Gjerset2, Svetlana Lebedeva, Ali Haghighi, Sally T. Turla and Dan Mercola

Sidney Kimmel Cancer Center, San Diego, California 92121

We have previously shown, by expression of a nonphosphorylatable dominant inhibitor mutant of c-Jun [cJun(S63A,S73A)], that activation of the NH2-terminal Jun kinase/stress-activated protein kinase by genotoxic damage is required for DNA repair. Here, we examine the consequences of inhibition of DNA repair on p53-induced apoptosis in T98G cells, which are devoid of endogenous wild-type p53. Relative to parental or wild-type c-Jun-expressing control cells, mutant Jun-expressing T98G clones show similar growth rates and plating efficiencies. However, these cells are unable to repair DNA (PCR-stop assays) and exhibit up to an 80-fold increased methotrexate-induced colony formation due to amplification of the dihydrofolate reductase gene. Moreover, the mutant c-Jun clones exhibit increased apoptosis and elevated bax:bcl2 ratios on expression of wild-type p53. These results indicate that inhibition of DNA repair leads to accumulation of DNA damage in tumor cells with unstable genomes and this, in turn, enhances p53-mediated apoptosis.




This article has been cited by other articles:


Home page
J Biol ChemHome page
K. J. Hughes, G. P. Meares, K. T. Chambers, and J. A. Corbett
Repair of Nitric Oxide-damaged DNA in {beta}-Cells Requires JNK-dependent GADD45{alpha} Expression
J. Biol. Chem., October 2, 2009; 284(40): 27402 - 27408.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
R. Rouget, Y. Auclair, M. Loignon, E. B. Affar, and E. A. Drobetsky
A Sensitive Flow Cytometry-based Nucleotide Excision Repair Assay Unexpectedly Reveals That Mitogen-activated Protein Kinase Signaling Does Not Regulate the Removal of UV-induced DNA Damage in Human Cells
J. Biol. Chem., February 29, 2008; 283(9): 5533 - 5541.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
G. Fritz and B. Kaina
Late Activation of Stress Kinases (SAPK/JNK) by Genotoxins Requires the DNA Repair Proteins DNA-PKcs and CSB
Mol. Biol. Cell, February 1, 2006; 17(2): 851 - 861.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
B. W. Ennis, K. E. Fultz, K. A. Smith, J. K. Westwick, D. Zhu, M. Boluro-Ajayi, G. K. Bilter, and B. Stein
Inhibition of Tumor Growth, Angiogenesis, and Tumor Cell Proliferation by a Small Molecule Inhibitor of c-Jun N-terminal Kinase
J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 325 - 332.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
A. MacLaren, E. J. Black, W. Clark, and D. A. F. Gillespie
c-Jun-Deficient Cells Undergo Premature Senescence as a Result of Spontaneous DNA Damage Accumulation
Mol. Cell. Biol., October 15, 2004; 24(20): 9006 - 9018.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
C.-K. Youn, M.-H. Kim, H.-J. Cho, H.-B. Kim, I.-Y. Chang, M.-H. Chung, and H. J. You
Oncogenic H-Ras Up-Regulates Expression of ERCC1 to Protect Cells from Platinum-Based Anticancer Agents
Cancer Res., July 15, 2004; 64(14): 4849 - 4857.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
Y. Huang, T. Tyler, N. Saadatmandi, C. Lee, P. Borgstrom, and R. A. Gjerset
Enhanced Tumor Suppression by a p14ARF/p53 Bicistronic Adenovirus through Increased p53 Protein Translation and Stability
Cancer Res., July 1, 2003; 63(13): 3646 - 3653.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
I. A. Vasilevskaya, T. V. Rakitina, and P. J. O'Dwyer
Geldanamycin and its 17-Allylamino-17-Demethoxy Analogue Antagonize the Action of Cisplatin in Human Colon Adenocarcinoma Cells: Differential Caspase Activation as a Basis for Interaction
Cancer Res., June 15, 2003; 63(12): 3241 - 3246.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
G. Mathonnet, C. Leger, J. Desnoyers, R. Drouin, J.-P. Therrien, and E. A. Drobetsky
UV wavelength-dependent regulation of transcription-coupled nucleotide excision repair in p53-deficient human cells
PNAS, June 10, 2003; 100(12): 7219 - 7224.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Hayakawa, C. Depatie, M. Ohmichi, and D. Mercola
The Activation of c-Jun NH2-terminal Kinase (JNK) by DNA-damaging Agents Serves to Promote Drug Resistance via Activating Transcription Factor 2 (ATF2)-dependent Enhanced DNA Repair
J. Biol. Chem., May 30, 2003; 278(23): 20582 - 20592.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.