Drosophila p53 is a structural and functional homolog of the tumor suppressor p53

Cell. 2000 Mar 31;101(1):91-101. doi: 10.1016/S0092-8674(00)80626-1.

Abstract

The importance of p53 in carcinogenesis stems from its central role in inducing cell cycle arrest or apoptosis in response to cellular stresses. We have identified a Drosophila homolog of p53 ("Dmp53"). Like mammalian p53, Dmp53 binds specifically to human p53 binding sites, and overexpression of Dmp53 induces apoptosis. Importantly, inhibition of Dmp53 function renders cells resistant to X ray-induced apoptosis, suggesting that Dmp53 is required for the apoptotic response to DNA damage. Unlike mammalian p53, Dmp53 appears unable to induce a G1 cell cycle block when overexpressed, and inhibition of Dmp53 activity does not affect X ray-induced cell cycle arrest. These data reveal an ancestral proapoptotic function for p53 and identify Drosophila as an ideal model system for elucidating the p53 apoptotic pathway(s) induced by DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / radiation effects
  • Binding Sites
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Drosophila melanogaster
  • G1 Phase
  • Genes, Tumor Suppressor*
  • Humans
  • Insect Proteins / chemistry
  • Insect Proteins / genetics
  • Insect Proteins / physiology*
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • GADD45 protein
  • Insect Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Tumor Suppressor Protein p53