HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis

Mol Cell. 1999 Nov;4(5):745-55. doi: 10.1016/s1097-2765(00)80385-8.

Abstract

We have identified a Drosophila homolog of Apaf-1 and ced-4, termed hac-1. Like mammalian APAF-1, HAC-1 can activate caspases in a dATP-dependent manner in vitro. During embryonic development, hac-1 is prominently expressed in regions where cells undergo natural death. Significantly, hac-1 transcription is also rapidly induced upon ionizing irradiation, similar to the proapoptotic gene reaper. Loss of hac-1 function causes reduced cell death, and reducing the dosage of hac-1 suppresses ectopic cell killing upon expression of the dcp-1 procaspase in the retina but has little effect on reaper, hid, and grim-mediated killing. Our data indicate that caspase activation and apoptosis in Drosophila are independently controlled by at least two distinct regulatory pathways that converge at the level of caspase activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis* / radiation effects
  • Apoptotic Protease-Activating Factor 1
  • Base Sequence
  • Caenorhabditis elegans Proteins*
  • Calcium-Binding Proteins / chemistry*
  • Caspases / metabolism
  • Cell Line
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / radiation effects
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • Eye / embryology
  • Eye / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Helminth Proteins / chemistry*
  • Insect Proteins / chemistry*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / physiology
  • Peptides / genetics
  • Peptides / physiology
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid
  • Transcriptional Activation / radiation effects

Substances

  • Apoptotic Protease-Activating Factor 1
  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • Ced-4 protein, C elegans
  • Drosophila Proteins
  • Enzyme Precursors
  • HID protein, Drosophila
  • Helminth Proteins
  • Insect Proteins
  • Neuropeptides
  • Peptides
  • Proteins
  • RNA, Messenger
  • dark protein, Drosophila
  • grim protein, Drosophila
  • rpr protein, Drosophila
  • Caspases

Associated data

  • GENBANK/AF196306