Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family

B W Richter; S S Mir; L J Eiben; J Lewis; S B Reffey; A Frattini; L Tian; S Frank; R J Youle; D L Nelson; L D Notarangelo; P Vezzoni; H O Fearnhead; C S Duckett

doi:10.1128/MCB.21.13.4292-4301.2001

Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family

Mol Cell Biol. 2001 Jul;21(13):4292-301. doi: 10.1128/MCB.21.13.4292-4301.2001.

Authors

B W Richter¹, S S Mir, L J Eiben, J Lewis, S B Reffey, A Frattini, L Tian, S Frank, R J Youle, D L Nelson, L D Notarangelo, P Vezzoni, H O Fearnhead, C S Duckett

Affiliation

¹ Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1578, USA.

Abstract

Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of specific caspases. Here, we describe the molecular cloning and characterization of a human gene related to ILP-1, termed ILP-2. Despite high homology to ILP-1, ILP-2 is encoded by a distinct gene, which in normal tissues is expressed solely in testis. In contrast to ILP-1, overexpression of ILP-2 had no protective effect on apoptosis mediated by Fas (also known as CD95) or tumor necrosis factor. However, ILP-2 potently inhibited apoptosis induced by overexpression of Bax or by coexpression of caspase 9 with Apaf-1, and preincubation of cytosolic extracts with ILP-2 abrogated caspase activation in vitro. A processed form of caspase 9 could be coprecipitated with ILP-2 from cells, suggesting a physical interaction between ILP-2 and caspase 9. Thus, ILP-2 is a novel IAP family member with restricted specificity for caspase 9.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Apoptosis Regulatory Proteins
Apoptosis*
Apoptotic Protease-Activating Factor 1
Blotting, Northern
Caspase 9
Caspase Inhibitors
Caspases / metabolism*
Cell Line
Cloning, Molecular
Enzyme Inhibitors / metabolism*
Genes, Reporter / genetics
Humans
Immunoblotting
Inhibitor of Apoptosis Proteins
Molecular Sequence Data
Plasmids / genetics
Plasmids / metabolism
Primates
Proteins / chemistry
Proteins / genetics
Proteins / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Sequence Alignment
Transfection
X-Linked Inhibitor of Apoptosis Protein
bcl-2-Associated X Protein

Substances

APAF1 protein, human
Apoptosis Regulatory Proteins
Apoptotic Protease-Activating Factor 1
BAX protein, human
BIRC8 protein, human
Caspase Inhibitors
Enzyme Inhibitors
FAIM protein, human
Inhibitor of Apoptosis Proteins
Proteins
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
Recombinant Fusion Proteins
X-Linked Inhibitor of Apoptosis Protein
XIAP protein, human
bcl-2-Associated X Protein
CASP9 protein, human
Caspase 9
Caspases

Associated data

GENBANK/AF164682