ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death protein Ced-3 is activated during Fas- and tumor necrosis factor-induced apoptosis

J Biol Chem. 1996 Jan 19;271(3):1621-5. doi: 10.1074/jbc.271.3.1621.

Abstract

Members of the ICE/ced-3 gene family have been implicated as components of the cell death pathway. Based on similarities with the structural prototype interleukin-1 beta-converting enzyme (ICE), family members are synthesized as proenzymes that are proteolytically processed to form active heterodimeric enzymes. In this report, we describe a novel member of this growing gene family, ICE-LAP3, which is closely related to the death effector Yama/CPP32/Apopain. Pro-ICE-LAP3 is a 35-kDa protein localized to the cytoplasm and expressed in a variety of tissues and cell lines. Overexpression of a truncated version of ICE-LAP3 (missing the pro-domain) induces apoptosis in MCF7 breast carcinoma cells. Importantly, upon receipt of a death stimulus, endogenous ICE-LAP3 is processed to its subunit forms, suggesting a physiological role in cell death. This is the first report to demonstrate processing of a native ICE/ced-3 family member during execution of the death program and the first description of the subcellular localization of an ICE/ced-3 family member.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Base Sequence
  • Breast Neoplasms
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins*
  • Caspase 7
  • Caspases*
  • Cell Line
  • Cysteine Endopeptidases*
  • DNA Primers
  • Female
  • Fetus
  • Gene Expression
  • Helminth Proteins / chemistry*
  • Helminth Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Multigene Family
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Protein Precursors / biosynthesis
  • Protein Precursors / metabolism
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Rats
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*
  • fas Receptor / pharmacology*

Substances

  • Caenorhabditis elegans Proteins
  • DNA Primers
  • Helminth Proteins
  • Protein Precursors
  • Proteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • CASP7 protein, human
  • Caspase 7
  • Caspases
  • Cysteine Endopeptidases
  • ced-3 protein, C elegans

Associated data

  • GENBANK/U39613