DOI: 10.1073/pnas.0736384100. <i>Drosophila</i> p53 preserves genomic stability by regulating cell death

Drosophila p53 preserves genomic stability by regulating cell death

10.1073/pnas.0736384100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

When animal cells are exposed to stressful conditions, the tumor suppressor protein p53 restrains growth by promoting an arrested cell cycle or initiating a cell death program. How these distinct fates are specified through the action of a single protein is not known. To study its functions in vivo we produced a targeted mutation at the Drosophila p53 ( Dmp53 ) locus. We show that Dmp53 is required for damage-induced apoptosis but not for cell-cycle arrest. Dmp53 function is also required for damage-induced transcription of two tightly linked cell death activators, reaper and sickle . When challenged by ionizing radiation, Dmp53 mutants exhibit radiosensitivity and genomic instability. Hence, elevated mutant loads were not caused by defective checkpoint functions but instead correlated with failures in p53-associated cell death. Our studies support the notion that core ancestral functions of the p53 gene family are intimately coupled to cell death as an adaptive response to maintain genomic stability.

Bibliography

Sogame, N., Kim, M., & Abrams, J. M. (2003). Drosophila p53 preserves genomic stability by regulating cell death. Proceedings of the National Academy of Sciences, 100(8), 4696â4701.

Authors 3

Naoko Sogame (first)
Misoo Kim (additional)
John M. Abrams (additional)

References 53 Referenced 132

10.1038/sj.onc.1203285
10.1016/S0092-8674(00)81871-1
K H Vousden Biochim Biophys Acta 1602, 47–59 (2002). / Biochim Biophys Acta by Vousden K H (2002)
10.1016/S0092-8674(00)00171-9
10.1023/A:1009659708549
10.1006/scbi.1998.0097
10.1038/79152
10.1093/emboj/19.18.4967
10.1038/370220a0
10.1016/0092-8674(91)90560-L
10.1126/science.256.5058.827
10.1126/science.8023157
10.1101/gad.7.12b.2556
10.1016/0092-8674(95)90039-X
10.1016/0092-8674(93)90500-P
10.1016/0092-8674(93)90499-G
10.1016/0092-8674(95)90513-8
10.1126/science.288.5468.1053
10.1016/S1097-2765(01)00213-1
10.1016/S1097-2765(01)00214-3
10.1128/MCB.15.6.3032
10.1074/jbc.275.6.3867
10.1038/38525
10.1073/pnas.96.25.14517
10.1016/S0092-8674(00)80627-3
10.1073/pnas.97.13.7301
10.1016/S0092-8674(00)80626-1
10.1002/j.1460-2075.1992.tb05183.x
10.1126/science.2144363
10.1126/science.7878469
10.1128/jvi.62.12.4737-4744.1988
10.1126/science.270.5238.983
10.1016/S0962-8924(99)01646-3
10.1006/dbio.1996.0296
10.1242/dev.129.6.1467
10.1093/genetics/157.3.1307
10.1126/science.288.5473.2013
10.1101/gad.9.14.1694
10.1101/gad.10.14.1773
10.1126/science.8171319
10.1016/S0960-9822(01)00658-3
10.1007/s004120050256
10.1101/gad.14.6.666
10.1093/genetics/90.3.531
10.1073/pnas.172382899
10.1101/gad.986602
10.1016/S0960-9822(01)00664-9
10.1016/S0960-9822(01)00657-1
10.1126/science.1065486
10.1016/S0014-5793(01)03103-9
G M Wahl, S P Linke, T G Paulson, L C Huang Cancer Surv 29, 183–219 (1997). / Cancer Surv by Wahl G M (1997)
10.1080/02841860152619106
10.1016/S1535-6108(02)00047-8

Dates

Type	When
Created	22 years, 4 months ago (April 15, 2003, 6:56 p.m.)
Deposited	3 years, 4 months ago (April 25, 2022, 10:02 p.m.)
Indexed	2 months, 4 weeks ago (June 4, 2025, 9:56 p.m.)
Issued	22 years, 5 months ago (April 2, 2003)
Published	22 years, 5 months ago (April 2, 2003)
Published Online	22 years, 5 months ago (April 2, 2003)
Published Print	22 years, 4 months ago (April 15, 2003)

Funders 0

None

BibTeX

@article{Sogame_2003, title={Drosophila p53 preserves genomic stability by regulating cell death}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0736384100}, DOI={10.1073/pnas.0736384100}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sogame, Naoko and Kim, Misoo and Abrams, John M.}, year={2003}, month=apr, pages={4696–4701} }

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  "abstract": "<jats:p>\n            When animal cells are exposed to stressful conditions, the tumor suppressor protein p53 restrains growth by promoting an arrested cell cycle or initiating a cell death program. How these distinct fates are specified through the action of a single protein is not known. To study its functions\n            <jats:italic>in vivo</jats:italic>\n            we produced a targeted mutation at the\n            <jats:italic>Drosophila p53</jats:italic>\n            (\n            <jats:italic>Dmp53</jats:italic>\n            ) locus. We show that Dmp53 is required for damage-induced apoptosis but not for cell-cycle arrest. Dmp53 function is also required for damage-induced transcription of two tightly linked cell death activators,\n            <jats:italic>reaper</jats:italic>\n            and\n            <jats:italic>sickle</jats:italic>\n            . When challenged by ionizing radiation,\n            <jats:italic>Dmp53</jats:italic>\n            mutants exhibit radiosensitivity and genomic instability. Hence, elevated mutant loads were not caused by defective checkpoint functions but instead correlated with failures in p53-associated cell death. Our studies support the notion that core ancestral functions of the p53 gene family are intimately coupled to cell death as an adaptive response to maintain genomic stability.\n          </jats:p>",
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