Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.
By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.
Department of Viral Oncology, Japanese Foundation for Cancer Research, Tokyo.
S
S
Kumar
M
M
Kinoshita
M
M
Noda
N G
NG
Copeland
N A
NA
Jenkins
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D053143:Caspase 2; D020169:Caspases; D016923:Cell Death / Q000235:genetics*; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005314:Embryonic and Fetal Development; D005260:Female; D005822:Genetic Vectors; D015801:Helminth Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D008297:Male; D008322:Mammals / Q000235:genetics; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C490360:CASP2 protein, human; C090208:Casp2 protein, mouse; D053143:Caspase 2; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1