红细胞分化去核因子:哺乳类红细胞终末分化/肿瘤抑制的调节因子家族及其相关基因的克隆  

Erythroid Differentiation Denucleation Factor:a Family of Erythroid Regulators for Mammalian Erythroid Terminal Differentiation/Tumor Suppression and the Cloning of Their Related Genes

作　　者：薛社普[1] 刘友华[1] 张世馥[1] 马文丽[1] 王鑫[1] 费仁仁[1] 杜权[1] 章正琰[1] 章静波[1] 陈克铨[1] 周建平[1] 马静[1] 韩代书[1] 

机构地区：[1]中国医学科学院中国协和医科大学基础医学研究所细胞生物室,北京100005

出　　处：《中国医学科学院学报》2000年第4期371-375,共5页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金!( 3 9670 3 64 )&&

摘　　要：本文报道哺乳类红细胞终末分化去核因子 (EDDF)调控恶性骨髓瘤细胞的分化以及与 EDDF相关的基因克隆的系列研究结果。以不同分化期哺乳类红细胞为研究对象 ,观察红细胞自然排核前后的细胞形态变化和与之互为对应的物质代谢的改变 ,分析 EDDF与终末分化、核浓缩及自然排核的可能关系 ;用自建的红细胞胞质体杂交模型 ,分别对红白血病和非红系的骨髓瘤细胞进行同种和异种的细胞杂交实验以验证 EDDF的作用规律。结果表明 ,哺乳类红细胞在终末分化不同阶段存在时相相关的分化去核因子家族。这些因子可调控不同分化阶段相关基因的活动 ,且呈时序性出现 ,与血红蛋白表达、细胞核停止分裂转向分化、核偏位、核浓 (固 )缩和自然去核等终末分化特征呈现明显的因果关系。 EDDF活性蛋白可逆转体外培养的肿瘤细胞系 (MEL,K5 6 2 )的恶性生长及诱导终末分化。在上述基础上分别采用不同的分离、提纯及基因克隆路线 ,从人和小鼠红细胞中连续克隆到 5种分化相关基因家族 (MEDDF,HEDDF- 1,HEDRF- 1,HEDRF- 2 ,HCNBP- 1)及其全长序列 ,并经 Gen Bank证实 ,它们均为无同源的新基因序列。The role of regulation of erythroid differentiation denucleation factor(EDDF)on mammalian erythroid differentiation and myeloma cell malignancy as well as cloning of their stage related genes were serially studied Through a series of cybrid and hybridization experiments between mammalian erythroid cells and erythroleukemia or non erythroid myeloma cells,we have demonstrated a novel family of erythroid regulators(EDDFs)in the mammalian differentiating erythroblasts which with an active peak occurred concomitantly with marked decreases in DNA,RNA and the nuclear anchoring vimentin IF,but increased in hemoglobin synthesis in cytoplasm prior to the denucleation process during terminal differentiation The results of cell fusion experiments verified that the supplement of regulators(EDDFs)was critical to the recovery of the originally lost features of terminal differentiation and the reversion of malignant phenotype of tumor cells Here we showed that the erythroid regulator family EDDFs were essential regulators for the sequential expression of stage related genes of erythroid terminal differentiation,and for the redifferentiation of tumor cells to express the originally inactive globe genes,repressed the oncogenes,and vimentin IF system,thus initiated nuclear condensation and denucleation The EDDF gene family consisted of MEDDF,HEDDF 1,HEDRF 1,HEDRF 2 and HCNBP 1 were cloned All were novel cDNA sequences that have been searched and registrated in GenBank They expressed varying in a stage specific manner,and acted on corresponding genes of terminal differentiation

关 键 词：终末分化 红细胞分化去核因子 调控 基因克隆 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学]