title: Zfrp8, the Drosophila ortholog of PDCD2, functions in lymph gland development and controls cell proliferation.
abstract: We have identified a new gene, Zfrp8, as being essential for hematopoiesis in Drosophila. Zfrp8 (Zinc finger protein RP-8) is the Drosophila ortholog of the PDCD2 (programmed cell death 2) protein of unknown function, and is highly conserved in all eukaryotes. Zfrp8 mutants present a developmental delay, lethality during larval and pupal stages and hyperplasia of the hematopoietic organ, the lymph gland. This overgrowth results from an increase in proliferation of undifferentiated hemocytes throughout development and is accompanied by abnormal differentiation of hemocytes. Furthermore, the subcellular distribution of gamma-Tubulin and Cyclin B is affected. Consistent with this, the phenotype of the lymph gland of Zfpr8 heterozygous mutants is dominantly enhanced by the l(1)dd4 gene encoding Dgrip91, which is involved in anchoring gamma-Tubulin to the centrosome. The overgrowth phenotype is also enhanced by a mutation in Cdc27, which encodes a component of the anaphase-promoting complex (APC) that regulates the degradation of cyclins. No evidence for an apoptotic function of Zfrp8 was found. Based on the phenotype, genetic interactions and subcellular localization of Zfrp8, we propose that the protein is involved in the regulation of cell proliferation from embryonic stages onward, through the function of the centrosome, and regulates the level and localization of cell-cycle components. The overproliferation of cells in the lymph gland results in abnormal hemocyte differentiation.
authors.affiliation: Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, 190 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Minakhina
authors.forename: Marina
authors.initials: M
authors.lastname: Druzhinina
authors.forename: Ruth
authors.initials: R
authors.lastname: Steward
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C503698:CycB protein, Drosophila; D019925:Cyclin A; D019926:Cyclin B; D029721:Drosophila Proteins; D014157:Transcription Factors; C522153:Zfrp8 protein, Drosophila; C109259:pnr protein, Drosophila