The Drosophila Caspase Inhibitor DIAP1 Is Essential for Cell Survival and Is Negatively Regulated by HID

Cell. 1999 Aug 20;98(4):453-63. doi: 10.1016/s0092-8674(00)81974-1.

Abstract

Drosophila Reaper (RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Based on these results, we propose that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP-caspase interactions and that DIAP1 is required to block apoptosis-inducing caspase activity. Supporting this hypothesis, we show that elimination of DIAP1 function results in global early embryonic cell death and a large increase in DIAP1-inhibitable caspase activity and that DIAP1 is still required for cell survival when expression of rpr, hid, and grim is eliminated.

Publication types

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

MeSH terms

  • Acridine Orange
  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Caspase Inhibitors*
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Epistasis, Genetic
  • Fluorescent Dyes
  • Genes, Lethal
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins / genetics
  • Insect Proteins / physiology*
  • Morphogenesis / genetics
  • Neuropeptides / genetics
  • Neuropeptides / physiology
  • Peptides / genetics
  • Peptides / physiology
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae / cytology

Substances

  • Caspase Inhibitors
  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • Fluorescent Dyes
  • HID protein, Drosophila
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins
  • Neuropeptides
  • Peptides
  • Recombinant Fusion Proteins
  • grim protein, Drosophila
  • rpr protein, Drosophila
  • Acridine Orange