[Erythroid differentiation denucleation factor: a family of erythroid regulators for mammalian erythroid terminal differentiation/tumor suppression and the cloning of their related genes].
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 registered in GenBank. They expressed varying in a stage specific manner, and acted on corresponding genes of terminal differentiation.
Xue
S
S
Department of Cell Biology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China. xuesp@public.bta.net.cn
Liu
Y
Y
Zhang
S
S
Ma
W
W
Wang
X
X
Fei
R
R
Du
Q
Q
Zhang
Z
Z
Zhang
J
J
Chen
K
K
Zhou
J
J
Ma
J
J
Han
D
D
D028341:Activins / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004900:Erythroblasts / Q000166:cytology*; D006801:Humans; D006822:Hybrid Cells; D028322:Inhibin-beta Subunits / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D011817:Rabbits; D014407:Tumor Cells, Cultured
C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits