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Hum Genet (1995) 95:641-644 y Springer-Verlag 1995 Sharad Kumar i Deborah L. White i Setsuo Takai Suzanne Turczynowicz i Christopher A. Juttner Timothy R Hughes Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms Received: 24 October 1994/Revised: 18 November 1994 Abstract Developmentally regulated mouse gene Nedd2 encodes a protein similar to the product of the nematode Caenorhabditis elegans cell death gene ced-3 and the mammalian interleukin- l[3-converting enzyme. Overex- pression of Nedd2 in cultured mammalian cells induces apoptosis that can be blocked by proto-oncogene BCL2. We have isolated cDNA clones for the human homologue of the mouse gene and, by using these as probes, mapped the human NEDD2 gene to 7q34-35 by fluorescence in situ hybridisation. The potential tumour suppressor func- tion of NEDD2 is discussed. Introduction By subtraction cloning, we have previously identified a set of mouse genes (named Neddl to Neddl0) with de- velopmentally down-regulated expression in the brain (Kumar et al. 1992). We have recently shown that one such gene, Nedd2, encodes a protein similar to the mam- malian interleukin-l~-converting enzyme (ICE) and the product of the cell death gene, ced-3, of Caenorhabditis elegans (Kumar et al. 1994). Both ICE and ced-3 encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells (Miura et al. 1993). Over- expression of Nedd2 in cultured cells also results in cell death by apoptosis; this is suppressed by the expression of the human BCL2 proto-oncogene indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans (Ku- mar et al. 1994). Recently, a human homologue (NEDD2) S. Kumar (t~) i D. L. White i S. Turczynowicz - C. A. Juttner T. P. Hughes Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Box 14, Rundle Mall Post Office, Adelaide, SA 5000, Australia S. Takai Department of Genetics, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo 162, Japan of the mouse Nedd2 gene (the mouse Nedd2 and human NEDD2 symbols used in this paper have been approved by the International Committee on Mouse Genetic Nomenclature and the HUGO Nomenclature Committee, respectively), which the authors call Ich-1, has also been shown to induce apoptosis in various cell lines (Wang et al. 1994). An alternately spliced form of NEDD2 mRNA, which encodes for a truncated protein (Ich-1 s), protects Rat-1 cells from serum-deprivation-induced cell death (Wang et al. 1994). During embryonic development, Nedd2 is highly expressed in several mouse tissues under- going high rates of apoptosis, such as the central nervous system and kidney (Kumar et al. 1994). These data sug- gest that Nedd2 is an important component of the mam- malian programmed cell death machinery. Oncogenes, such as BCL2, act by enhancing cell via- bility (reviewed in Korsmeyer 1992), whereas tumour suppressor genes, such as p53, may be required for nor- mal physiological cell death to occur (Yonish-Rouach et al. 1992: Shaw et al. 1992). Therefore, genes such as Nedd2 and ICE, which regulate cell death in a positive fashion, probably function as tumour suppressor genes and may be important in multistep carcinogenesis. We have previously localised the mouse Nedd2 gene to the proximal region of chromosome 6 (Kumar et al. 1994). This region of mouse chromosome 6 shares a region of homology with human chromosome arm 7q. Structural abnormalities involving 7q frequently occur in a number of human haematological neoplasms and the presence of a candidate tumour suppressor gene on 7q has been sug- gested (Neuman et al. 1992; Johansson et al. 1993). Therefore, it is of interest to determine the chromosomal localisation of the human NEDD2 gene. In the present study, we have isolated human NEDD2 cDNA clones and, using these as probes, have mapped the gene to human chromosome region 7q34-35 by fluorescence in situ hy- bridisation (FISH).