Minakhina Svetlana, Druzhinina Marina, Steward Ruth
Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, 190 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Development. 2007 Jul;134(13):2387-96. doi: 10.1242/dev.003616. Epub 2007 May 23.
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.
我们已鉴定出一个新基因Zfrp8，它对果蝇的造血作用至关重要。Zfrp8（锌指蛋白RP - 8）是功能未知的PDCD2（程序性细胞死亡2）蛋白在果蝇中的直系同源物，并且在所有真核生物中高度保守。Zfrp8突变体表现出发育延迟、幼虫和蛹期致死以及造血器官淋巴腺的增生。这种过度生长是由于未分化血细胞在整个发育过程中的增殖增加所致，并伴有血细胞的异常分化。此外，γ - 微管蛋白和细胞周期蛋白B的亚细胞分布也受到影响。与此一致的是，编码参与将γ - 微管蛋白锚定到中心体的Dgrip91的l(1)dd4基因，可使Zfpr8杂合突变体的淋巴腺表型显著增强。编码后期促进复合物（APC）组分（调节细胞周期蛋白降解）的Cdc27突变也增强了过度生长表型。未发现Zfrp8具有凋亡功能的证据。基于Zfrp8的表型、遗传相互作用和亚细胞定位，我们提出该蛋白从胚胎阶段起就通过中心体的功能参与细胞增殖的调控，并调节细胞周期组分的水平和定位。淋巴腺中细胞的过度增殖导致血细胞异常分化。
