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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. Export

Genes and Development, Vol. 8 (1994), pp. 1613-1626.

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amino_acid_sequence article base_sequence brain_embryology brain_metabolism c48d12 caenorhabditis_elegans caenorhabditis_elegans_cytology caenorhabditis_elegans_embryology caenorhabditis_elegans_genetics ced-3 celegans c_elegans cell_death_genetics cells_cultured chromosome_mapping cloning_molecular cysteine_proteinases_biosynthesis cysteine_proteinases_genetics elegans embryo fetal_development genetic_vectors helminth_proteins_genetics in_situ_hybridization mammals_genetics mice_genetics molecular_sequence_data nematode organ_specificity sequence_homology_amino_acid transfection wormbase

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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.


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