Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis

Nat Cell Biol. 2002 Jun;4(6):451-6. doi: 10.1038/ncb800.

Abstract

In Drosophila melanogaster, apoptosis is controlled by the integrated actions of the Grim-Reaper (Grim-Rpr) and Drosophila Inhibitor of Apoptosis (DIAP) proteins (reviewed in refs 1 4). The anti-apoptotic DIAPs bind to caspases and inhibit their proteolytic activities. DIAPs also bind to Grim-Rpr proteins, an interaction that promotes caspase activity and the initiation of apoptosis. Using a genetic modifier screen, we identified four enhancers of grim-reaper-induced apoptosis that all regulate ubiquitination processes: uba-1, skpA, fat facets (faf), and morgue. Strikingly, morgue encodes a unique protein that contains both an F box and a ubiquitin E2 conjugase domain that lacks the active site Cys required for ubiquitin linkage. A reduction of morgue activity suppressed grim-reaper-induced cell death in Drosophila. In cultured cells, Morgue induced apoptosis that was suppressed by DIAP1. Targeted morgue expression downregulated DIAP1 levels in Drosophila tissue, and Morgue and Rpr together downregulated DIAP1 levels in cultured cells. Consistent with potential substrate binding functions in an SCF ubiquitin E3 ligase complex, Morgue exhibited F box-dependent association with SkpA and F box-independent association with DIAP1. Morgue may thus have a key function in apoptosis by targeting DIAP1 for ubiquitination and turnover.

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 / physiology*
  • Cells, Cultured
  • Drosophila
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins / metabolism
  • Ligases / chemistry*
  • Ligases / genetics
  • Molecular Sequence Data
  • Neuropeptides / metabolism*
  • Peptides / metabolism*
  • Protein Structure, Tertiary
  • SKP Cullin F-Box Protein Ligases*
  • Ubiquitin / metabolism
  • Ubiquitin-Conjugating Enzymes

Substances

  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • Eye Proteins
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins
  • Neuropeptides
  • Peptides
  • SkpA protein, Drosophila
  • Ubiquitin
  • grim protein, Drosophila
  • morgue protein, Drosophila
  • rpr protein, Drosophila
  • Ubiquitin-Conjugating Enzymes
  • SKP Cullin F-Box Protein Ligases
  • Ligases

Associated data

  • GENBANK/AY078386