Abstract
The p53 tumour suppressor plays central role in the maintenance of genome integrity. P53 deficient fruit flies are highly sensitive to ionizing radiation (IR) and show genome instability suggesting that the Drosophila melanogaster p53 (Dmp53) is necessary for the proper damage response upon IR. We found that Dmp53 null fruit flies are highly sensitive to ultraviolet radiation (UV) as well. We analyzed the expression levels of apoptotic genes in wild type and Dmp53 null mutant animals after UV or IR using quantitative real-time RT-PCR. Ark (Apaf-Irelated killer) was induced in a Dmp53-dependent way upon UV treatment but not by IR, hid (head involution defective/ wrinkled) was induced upon both types of DNA damage, while reaper was induced only upon IR but not UV treatment. Using microarray analysis we identified several further genes that are activated upon UV irradiation in the presence of wild type Dmp53 only. Some but not all of these genes show Dmp53-dependent activation upon IR treatment as well. These results suggest that Dmp53 activates distinct cellular pathways through regulation of different target genes after different types of DNA damage.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aihara, H., Nakagawa, T., Yasui, K., Ohta, T., Hirose, S., Dhomae, N., Takio, K., Kaneko, M., Takeshima, Y., Muramatsu, M., Ito, T. (2004) Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. Genes Dev. 18, 877–888.
Allison, S. J., Milner, J. (2003) Loss of p53 has site-specific effects on histone H3 modification, including serine 10 phosphorylation important for maintenance of ploidy Cancer Res. 63, 6674–6679.
Asha, H., Nagy, I., Kovacs, G., Stetson, D., Ando, I., Dearolf C. R. (2003) Analysis of Ras-induced overproliferation in Drosophila hemocytes. Genetics 163, 203–215.
Ashcroft, M., Taya, Y., Vousden, K. H. (2000) Stress signals utilize multiple pathways to stabilize p53. Mol. Cell. Biol. 20, 3224–3233.
Bang, A. G., Kintner, C. (2000) Rhomboid and Star facilitate presentation and processing of the Drosophila TGF-alpha homolog Spitz. Genes Dev. 14, 177–186.
Barbosa, V., Yamamoto, R. R., Henderson, D. S., Glover, D. M. (2000) Mutation of a Drosophila gamma tubulin ring complex subunit encoded by discs degenerate-4 differentially disrupts centroso-mal protein localization. Genes Dev. 14, 3126–3139.
Brodsky, M. H., Nordstrom, W., Tsang, G., Kwan, E., Rubin, G. M., Abrams, J. M. (2000) Drosophila p53 binds a damage response element at the reaper locus. Cell. 101, 103–113.
Brodsky, M. H., Weinert, B. T., Tsang, G., Rong, Y. S., McGinnis, N. M, Golic, K. G, Rio, D. C., Rubin, G. M. (2004) Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol. Cell. Biol. 24, 1219–1231.
Brooks, C. L., Gu, W. (2006) p53 ubiquitination: Mdm2 and beyond. Mol. Cell. 21, 307–315.
Dong, X., Tsuda, L., Zavitz, K. H., Lin, M., Li, S., Carthew, R. W., Zipursky, S. L. (1999) ebi regulates epidermal growth factor receptor signaling pathways in Drosophila. Genes Dev. 13, 954–965.
FlyBase, C., Swiss-Prot, P. M., InterPro, P. M. (2004) Gene ontology annotation in FlyBase through association of InterPro records with GO terms, https://doi.org/www.flybase.org
Gunawardane, R. N., Martin, O. C., Cao, K., Zhang, L, Dej, K., Iwamatsu, A., Zheng, Y. (2000) Characterization and reconstitution of Drosophila gamma-tubulin ring complex subunits. J. Cell. Biol. 151, 1513–1524.
Hay, B. A., Huh, J. R., Guo, M. (2004) The genetics of cell death: approaches, insights and opportunities in Drosophila. Nat. Rev. Genet. 5, 911–922.
Jassim, O. W., Fink, J. L., Cagan, R. L. (2003) Dmp53 protects the Drosophila retina during a devel-opmentally regulated DNA damage response. EMBO J. 22, 5622–5632.
Jin, S., Martinek, S., Joo, W. S., Wormian, J. R., Mirkovic, N., Sali, A., Yandell, M. D., Pavletich, N. P., Young, M. W., Levine, A. J. (2000) Identification and characterization of a p53 homologue in Drosophila melanogaster Proc. Natl. Acad Sci. USA. 97, 7301–7306.
Johnson, M. R., Wang, K., Smith, J. B., Heslin, M. J., Diasio, R. B. (2000) Quantitation of dihy-dropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction. Anal. Biochem. 278, 175–184.
Kanuka, H., Sawamoto, K., Inohara, N., Matsuno, K., Okano, H., Miura, M. (1999) Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator. Mol. Cell. 4, 757–769.
Kapoor, M., Lozano, G. (1998) Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation. Proc. Natl. Acad. Sci. USA. 95, 2834–2837.
Kurada, P., White, K. (1998) Ras promotes cell survival in Drosophila by downregulating hid expression. Cell. 95, 319–329.
Lane, D. P. (1992) Cancer. p53, guardian of the genome. Nature 358, 15–16.
Latonen, L., Laiho, M. (2005) Cellular UV damage responses-functions of tumor suppressor p53. Biochim. Biophys. Acta 1755, 71–89.
Lee, C. Y., Clough, E. A., Yellon, P., Teslovich, T. M., Stephan, D. A., Baehrecke, E. H. (2003) Genome-wide analyses of steroid- and radiation-triggered programmed cell death in Drosophila. Curr Biol. 13, 350–357.
Lee, J. H., Lee, E., Park, J., Kim, E., Kim, J., Chung, J. (2003) In vivo p53 function is indispensable for DNA damage-induced apoptotic signaling in Drosophila. FEBS Lett. 550, 5–10.
Leng, R. P., Lin, Y., Ma, W., Wu, H., Lemmers, B., Chung, S., Parant, J. M., Lozano, G., Hakem, R., Benchimol, S. (2003) Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell. 112, 779–791.
Li, X., Scuderi, A., Letsou, A., Virshup, D. M. (2002) B56-associated protein phosphatase 2A is required for survival and protects from apoptosis in Drosophila melanogaster. Mol. Cell. Biol. 22, 3674–3684.
Ljungman, M. (2000) Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress. Neoplasia 2, 208–225.
Martin, D. N., Baehrecke, E. H. (2004) Caspases function in autophagic programmed cell death in Drosophila. Development 131, 275–284.
Matsuzawa, S. I., Reed, J. C. (2001) Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol. Cell. 7, 915–926.
McKay, B. C., Chen, F., Perumalswami, C. R., Zhang, F., Ljungman, M. (2000) The tumor suppressor p53 can both stimulate and inhibit ultraviolet light-induced apoptosis. Mol. Biol. Cell. 11, 2543–2551.
McKay, B. C., Stubbert, L. J., Fowler, C. C., Smith, J. M., Cardamore, R. A., Spronck, J. C. (2004) Regulation of ultraviolet light-induced gene expression by gene size. Proc. Natl. Acad. Sci. USA 101, 6582–6586.
Ollmann, M., Young, L. M., Di Como, C. J., Karim, F., Belvin, M., Robertson, S., Whittaker, K., Demsky, M., Fisher, W. W., Buchman, A., Duyk, G., Friedman, L., Prives, C., Kopczynski, C. (2000) Drosophila p53 is a structural and functional homolog of the tumor suppressor p53. Cell. 101, 91–101.
Peters, M., DeLuca, C., Hirao, A., Stambolic, V., Potter, J., Zhou, L., Liepa, J., Snow, B., Arya, S., Wong, J., Bouchard, D., Binari, R., Manoukian, A. S., Mak, T. W. (2002) Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila. Proc. Natl. Acad. Sci. USA 99, 11305–11310.
Peterson, C., Carney, G. E., Taylor, B. J., White, K. (2002) reaper is required for neuroblast apoptosis during Drosophila development. Development 129, 1467–1476.
Puskas, L. G., Nagy, Z. B., Giricz, Z., Onody, A., Csonka, C., Kitajka, K., Hackler, L. Jr., Zvara, A., Ferdinandy, P. (2004) Cholesterol diet-induced hyperlipidemia influences gene expression pattern of rat hearts: a DNA microarray study. FEES Lett. 562, 99–104.
Quandt, K., Frech, K., Karas, H., Wingender, E., Werner, T. (1995) MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res. 23, 4878–4884.
Rebollar, E., Valadez-Graham, V., Vazquez, M., Reynaud, E., Zurita, M. (2006) Role of the p53 homologue from Drosophila melanogaster in the maintenance of histone H3 acetylation and response to UV-light irradiation. FEBS Lett. 580, 642–648.
Rodriguez, A., Oliver, H., Zou, H., Chen, P., Wang, X., Abrams, J. M. (1999) Dark is Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway. Nat. Cell Biol. 1, 272–279.
Rong, Y. S., Titen, S. W., Xie, H. B., Golic, M. M., Bastiani, M., Bandyopadhyay, P., Olivera, B. M., Brodsky, M., Rubin, G. M., Golic, K. G. (2002) Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev. 16, 1568–1581.
Rozen, S., Skaletsky, H. J. (2000) Primer3 on the WWW for general users and for biologist programmers. Journal, 365–386.
Rubbi, C. P., Milner, J. (2003) p53 is a chromatin accessibility factor for nucleotide excision repair of DNA damage. EMBOJ. 22, 975–986.
Sogame, N., Kim, M., Abrams, J. M. (2003) Drosophila p53 preserves genomic stability by regulating cell death. Proc. Natl. Acad. Sci. USA 100, 4696–4701.
Van Hoof, C., Goris, J. (2003) Phosphatases in apoptosis: to be or not to be, PP2A is in the heart of the question. Biochim. Biophys. Acta 1640, 97–104.
Vanolst, L., Fromental-Ramain, C., Ramain, P. (2005) Toutatis, a TIP5-related protein, positively regulates Pannier function during Drosophila neural development. Development 132, 4327 1338.
Vousden, K. H., Lu, X. (2002) Live or let die: the cell’s response to p53. Nat. Rev. Cancer 2, 594–604.
Zhao, R., Gish, K., Murphy, M., Yin, Y, Notterman, D., Hoffman, W. H., Tom, E., Mack, D. H., Levine, A. J. (2000) Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. Genes Dev. 14, 981–993.
Zhou, L., Song, Z., Tittel, J., Steller, H. (1999) HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis. Mol. Cell. 4, 745–755.
Zhou, L., Steller, H. (2003) Distinct pathways mediate UV-induced apoptosis in Drosophila embryos. Dev. Cell. 4, 599–605.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
About this article
Cite this article
Ujfaludi, Z., Boros, I.M. & Bálint, É. Different Sets of Genes are Activated by P53 Upon UV or Ionizing Radiation in Drosophila Melanogaster. BIOLOGIA FUTURA 58 (Suppl 1), 65–79 (2007). https://doi.org/10.1556/ABiol.58.2007.Suppl.6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1556/ABiol.58.2007.Suppl.6