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  • Original Article
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p53 directs focused genomic responses in Drosophila

Oncogene volume 26, pages 5184–5193 (2007)Cite this article

Abstract

p53 is a fundamental determinant of cancer susceptibility and other age-related pathologies. Similar to mammalian counterparts, Drosophila p53 integrates stress signals and elicits apoptotic responses that maintain genomic stability. To illuminate core-adaptive functions controlled by this gene family, we examined the Drosophila p53 regulatory network at a genomic scale. In development, the absence of p53 impacted constitutive expression for a surprisingly broad scope of genes. By contrast, stimulus-dependent responses governed by Drosophila p53 were limited in scope. The vast majority of stress responders were induced and p53 dependent (RIPD) genes. The signature set of 29 ‘high stringency’ RIPD genes identified here were enriched for intronless loci, with a non-uniform distribution that includes a recently evolved cluster unique to Drosophila melanogaster. Two RIPD genes, with known and unknown biochemical activities, were functionally examined. One RIPD gene, designated XRP1, maintains genome stability after genotoxic challenge and prevents cell proliferation upon induced expression. A second gene, RnrL, is an apoptogenic effector required for caspase activation in a model of p53-dependent killing. Together, these studies identify ancient and convergent features of the p53 regulatory network.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

IR:

ionizing radiation

RnrL:

ribonucleotide reductase large subunit

RnrS:

ribonucleotide reductase small subunit

RIPD:

radiation-induced p53-dependent

References

  • Bae BI, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y et al. (2005). p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 47: 29–41.

    Article  CAS  PubMed  Google Scholar 

  • Bauer JH, Poon PC, Glatt-Deeley H, Abrams JM, Helfand SL . (2005). Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span. Curr Biol 15: 2063–2068.

    Article  CAS  PubMed  Google Scholar 

  • Blanchette M, Labourier E, Green RE, Brenner SE, Rio DC . (2004). Genome-wide analysis reveals an unexpected function for the Drosophila splicing factor U2AF50 in the nuclear export of intronless mRNAs. Mol Cell 14: 775–786.

    Article  CAS  PubMed  Google Scholar 

  • Brodsky MH, Nordstrom W, Tsang G, Kwan E, Rubin GM, Abrams JM . (2000). Drosophila p53 binds a damage response element at the reaper locus. Cell 101: 103–113.

    Article  CAS  PubMed  Google Scholar 

  • Brodsky MH, Weinert BT, Tsang G, Rong YS, McGinnis NM, Golic KG et al. (2004). Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol Cell Biol 24: 1219–1231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y . (2000). Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406: 855–862.

    Article  CAS  PubMed  Google Scholar 

  • Chen P, Ho SI, Shi Z, Abrams JM . (2004). Bifunctional killing activity encoded by conserved reaper proteins. Cell Death Differ 11: 704–713.

    Article  CAS  PubMed  Google Scholar 

  • Chew SK, Akdemir F, Chen P, Lu WJ, Mills K, Daish T et al. (2004). The apical caspase dronc governs programmed and unprogrammed cell death in Drosophila. Dev Cell 7: 897–907.

    Article  CAS  PubMed  Google Scholar 

  • Colombani J, Polesello C, Josue F, Tapon N . (2006). Dmp53 activates the Hippo pathway to promote cell death in response to DNA damage. Curr Biol 16: 1453–1458.

    Article  CAS  PubMed  Google Scholar 

  • Courgeon AM . (1972). Effects of - and -ecdysone on in vitro diploid cell multiplication in Drosophila melanogaster. Nat New Biol 238: 250–251.

    Article  CAS  PubMed  Google Scholar 

  • Daish TJ, Mills K, Kumar S . (2004). Drosophila caspase DRONC is required for specific developmental cell death pathways and stress-induced apoptosis. Dev Cell 7: 909–915.

    Article  CAS  PubMed  Google Scholar 

  • Dorstyn L, Colussi PA, Quinn LM, Richardson H, Kumar S . (1999). DRONC, an ecdysone-inducible Drosophila caspase. Proc Natl Acad Sci USA 96: 4307–4312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Echalier G, Ohanessian A . (1970). In vitro culture of Drosophila melanogaster embryonic cells. In Vitro 6: 162–172.

    Article  CAS  PubMed  Google Scholar 

  • Jin S, Kalkum M, Overholtzer M, Stoffel A, Chait BT, Levine AJ . (2003). CIAP1 and the serine protease HTRA2 are involved in a novel p53-dependent apoptosis pathway in mammals. Genes Dev 17: 359–367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kauppila S, Maaty WS, Chen P, Tomar RS, Eby MT, Chapo J et al. (2003). Eiger and its receptor, Wengen, comprise a TNF-like system in Drosophila. Oncogene 22: 4860–4867.

    Article  CAS  PubMed  Google Scholar 

  • Lee CY, Clough EA, Yellon P, Teslovich TM, Stephan DA, Baehrecke EH . (2003a). Genome-wide analyses of steroid- and radiation-triggered programmed cell death in Drosophila. Curr Biol 13: 350–357.

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Lee E, Park J, Kim E, Kim J, Chung J . (2003b). In vivo p53 function is indispensable for DNA damage-induced apoptotic signaling in Drosophila. FEBS Lett 550: 5–10.

    Article  CAS  PubMed  Google Scholar 

  • Lu WJ, Abrams JM . (2006). Lessons from p53 in non-mammalian models. Cell Death Differ 13: 909–912.

    Article  CAS  PubMed  Google Scholar 

  • Martins LM, Iaccarino I, Tenev T, Gschmeissner S, Totty NF, Lemoine NR et al. (2002). The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem 277: 439–444.

    Article  CAS  PubMed  Google Scholar 

  • Nakano K, Balint E, Ashcroft M, Vousden KH . (2000). A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene 19: 4283–4289.

    Article  CAS  PubMed  Google Scholar 

  • Nordstrom W, Abrams JM . (2000). Guardian ancestry: fly p53 and damage-inducible apoptosis. Cell Death Differ 7: 1035–1038.

    Article  CAS  PubMed  Google Scholar 

  • Nordstrom W, Chen P, Steller H, Abrams JM . (1996). Activation of the reaper gene during ectopic cell killing in Drosophila. Dev Biol 180: 213–226.

    Article  CAS  PubMed  Google Scholar 

  • Peters M, DeLuca C, Hirao A, Stambolic V, Potter J, Zhou L et al. (2002). Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila. Proc Natl Acad Sci USA 99: 11305–11310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakharkar MK, Kangueane P . (2004). Genome SEGE: a database for ‘intronless’ genes in eukaryotic genomes. BMC Bioinformatics 5: 67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharpless NE, DePinho RA . (2002). p53: good cop/bad cop. Cell 110: 9–12.

    Article  CAS  PubMed  Google Scholar 

  • Sogame N, Kim M, Abrams JM . (2003). Drosophila p53 preserves genomic stability by regulating cell death. Proc Natl Acad Sci USA 100: 4696–4701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K et al. (2000). A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404: 42–49.

    Article  CAS  PubMed  Google Scholar 

  • Verhagen AM, Silke J, Ekert PG, Pakusch M, Kaufmann H, Connolly LM et al. (2002). HtrA2 promotes cell death through its serine protease activity and its ability to antagonise inhibitor of apoptosis proteins. J Biol Chem 277: 445–454.

    Article  CAS  PubMed  Google Scholar 

  • Vousden KH, Prives C . (2005). P53 and prognosis: new insights and further complexity. Cell 120: 7–10.

    CAS  PubMed  Google Scholar 

  • Wu G, Chai J, Suber TL, Wu JW, Du C, Wang X et al. (2000). Structural basis of IAP recognition by Smac/DIABLO. Nature 408: 1008–1012.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Nichole Link, Muskaan Behl and Brad Riek for technical assistance and Margaret Hickson for administrative excellence. This work was supported by the NIH (RO1GMO72124) and a Research Scholar award to JMA from the American Cancer Society. Raw data and related files are available at GEO using accession numbers GSE2780 and GSE3072.

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Author notes

  1. J Chapo

    Present address: 3Current address: Myogen Inc., Westminster, CO 80021,USA.,

  2. F Akdemir, A Christich and N Sogame: These three authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA

    F Akdemir, A Christich, N Sogame, J Chapo & J M Abrams

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  1. F Akdemir
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  2. A Christich
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Correspondence to J M Abrams.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Akdemir, F., Christich, A., Sogame, N. et al. p53 directs focused genomic responses in Drosophila. Oncogene 26, 5184–5193 (2007). https://doi.org/10.1038/sj.onc.1210328

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