p53 directs focused genomic responses in Drosophila

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

Research output: Contribution to journalArticle

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5184-5193
Number of pages10
JournalOncogene
Volume26
Issue number36
DOIs
StatePublished - Aug 9 2007

Keywords

  • Apoptosis
  • Cell death
  • Drosophila
  • Radiation
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'p53 directs focused genomic responses in Drosophila'. Together they form a unique fingerprint.

  • Cite this

    Akdemir, F., Christich, A., Sogame, N., Chapo, J., & Abrams, J. M. (2007). p53 directs focused genomic responses in Drosophila. Oncogene, 26(36), 5184-5193. https://doi.org/10.1038/sj.onc.1210328