Molecular Biology of the Cell

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McKay, B. C.
Right arrow Articles by Ljungman, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McKay, B. C.
Right arrow Articles by Ljungman, M.

Vol. 11, Issue 8, 2543-2551, August 2000

The Tumor Suppressor p53 Can Both Stimulate and Inhibit Ultraviolet Light-induced Apoptosis

Bruce C. McKay,*dagger Feng Chen,* Chithra R. Perumalswami,* Fenfen Zhang,* and Mats Ljungman*Dagger §

 *Department of Radiation Oncology, Division of Cancer Biology, University of Michigan Comprehensive Cancer Center, and  Dagger Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0936

We have previously shown that the tumor suppressor p53 can play a protective role against UV-induced apoptosis in human fibroblasts. In the present study, we investigated whether the protective function of p53 expression is established before or after UV irradiation. Using a stable human cell line expressing a murine temperature-sensitive p53 in which p53 function could be tightly and reversibly regulated, we found that functional p53 stimulated the induction of apoptosis when expressed for as little as 4-12 h after UV irradiation and that this induction was not dependent on de novo protein synthesis. In contrast, expression of p53 for 12 h or more before UV irradiation reduced the extent of apoptosis even when functional p53 expression was maintained after irradiation. The protection conferred by p53 required ongoing protein synthesis and correlated with enhanced recovery of mRNA synthesis. Together, these results suggest that p53 induces distinct proapoptotic and antiapoptotic signals and that these opposing activities can be separated both temporally and by their requirement for de novo protein synthesis. These findings may have important implications for the refinement of gene therapy approaches combining p53 with pharmacological agents that target transcription or translation.

dagger Present address: Ottawa Regional Cancer Centre, Ottawa, ON, Canada, K1H 8L6.

§ Corresponding author. E-mail address: ljungman{at}umich.edu.

Molecular Biology of the Cell
Vol. 11, 2543-2551, August 2000
Copyright © 2000 by The American Society for Cell Biology


This article has been cited by other articles:


Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
A. B. Salmon, M. Ljungman, and R. A. Miller
Cells From Long-Lived Mutant Mice Exhibit Enhanced Repair of Ultraviolet Lesions
J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2008; 63(3): 219 - 231.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Gu, R. P. Singh, S. Dhanalakshmi, S. Mohan, and R. Agarwal
Differential effect of silibinin on E2F transcription factors and associated biological events in chronically UVB-exposed skin versus tumors in SKH-1 hairless mice.
Mol. Cancer Ther., August 1, 2006; 5(8): 2121 - 2129.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Wu, J. A. Roth, H. Zhao, S. Luo, Y.-L. Zheng, S. Chiang, and M. R. Spitz
Cell Cycle Checkpoints, DNA Damage/Repair, and Lung Cancer Risk
Cancer Res., January 1, 2005; 65(1): 349 - 357.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. J. M. Murphy, M. D. Galigniana, Y. Morishima, J. M. Harrell, R. P. S. Kwok, M. Ljungman, and W. B. Pratt
Pifithrin-{alpha} Inhibits p53 Signaling after Interaction of the Tumor Suppressor Protein with hsp90 and Its Nuclear Translocation
J. Biol. Chem., July 16, 2004; 279(29): 30195 - 30201.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. D. Galigniana, J. M. Harrell, H. M. O'Hagen, M. Ljungman, and W. B. Pratt
Hsp90-binding Immunophilins Link p53 to Dynein During p53 Transport to the Nucleus
J. Biol. Chem., May 21, 2004; 279(21): 22483 - 22489.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. C. McKay, L. J. Stubbert, C. C. Fowler, J. M. Smith, R. A. Cardamore, and J. C. Spronck
Regulation of ultraviolet light-induced gene expression by gene size
PNAS, April 27, 2004; 101(17): 6582 - 6586.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
S. Yanamadala and M. Ljungman
Potential Role of MLH1 in the Induction of p53 and Apoptosis by Blocking Transcription on Damaged DNA Templates
Mol. Cancer Res., August 1, 2003; 1(10): 747 - 754.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
M. L. Smith and Y. R. Seo
p53 regulation of DNA excision repair pathways
Mutagenesis, March 1, 2002; 17(2): 149 - 156.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Dubrez, J.-L. Coll, A. Hurbin, E. Solary, and M.-C. Favrot
Caffeine Sensitizes Human H358 Cell Line to p53-mediated Apoptosis by Inducing Mitochondrial Translocation and Conformational Change of BAX Protein
J. Biol. Chem., October 12, 2001; 276(42): 38980 - 38987.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. Ljungman
Individual Variation in p53 Responsiveness
J Natl Cancer Inst, January 17, 2001; 93(2): 82 - 83.
[Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]