Drosophila awdK-pn, a homologue of the metastasis suppressor gene nm23, suppresses the Tum-1 haematopoietic oncogene.
The human nm23-H1 gene is a suppressor of solid tumour metastasis in some types of cancer. It is known that nm23 genes encode nucleoside diphosphate kinase polypeptides, but the regulatory pathways involving Nm23 are unclear. One approach to understanding nm23 function is to identify loci which interact with nm23. The Drosophila awd gene, a homologue of nm23, provides a model system for this genetic analysis. We report that the dominant awdK-pn allele suppresses haematopoietic defects associated with the Tum-l oncogene. Premature differentiation and aggregation of Tum-l blood cells is reduced by awdK-pn, resulting in an increased survival of Tum-l hemizygotes. Tum-l lethality is also suppressed by pn mutations, indicating the existence of a haematopoietic regulatory pathway involving the Tum-l, AwdK-pn and Pn proteins.
Zinyk
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DL
Developmental Genetics Group, Dana Farber Cancer Institute, Boston, Massachusetts.
McGonnigal
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BG
Dearolf
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CR
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D004742:Enhancer Elements, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017344:Genes, Insect; D005804:Genes, Lethal; D005808:Genes, Recessive; D016147:Genes, Tumor Suppressor; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007301:Insect Hormones / Q000235:genetics* / Q000502:physiology; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D009857:Oncogenes; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D013045:Species Specificity
D029721:Drosophila Proteins; D007301:Insect Hormones; D011505:Protein-Tyrosine Kinases; D009701:Nucleoside-Diphosphate Kinase; C061642:awd protein, Drosophila