Constitutive expression of GATA-1 interferes with the cell-cycle regulation
Constitutive expression of GATA-1 interferes with the cell-cycle regulation
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DOI：
10.1182/blood.v87.9.3711.bloodjournal8793711
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发表时间：
1996-05-01
期刊：
影响因子：
20.3
通讯作者：
Dumenil, D
中科院分区：
文献类型：
--
作者：
Dubart, A;Romeo, PH;Dumenil, D
加塔-1主要在红系分化过程中表达，可调节红系细胞后期特异性表达的基因，保护红系细胞免于凋亡，提示其可能干扰细胞周期。通过在NIH 3 T3成纤维细胞中表达逆转录病毒转导的人加塔-1 cDNA，我们已经证明，单独的加塔-1不能反式激活这些非红系细胞中的红系特异性靶基因。然而，加塔-1表达对这些成纤维细胞的增殖具有显著影响。表达加塔-1的成纤维细胞的克隆效率得以维持，但它们的S期大大延长，它们的G1和G2/M期减少，实质上损害了它们的增殖。当在低血清浓度下培养48小时时，表达加塔-1的成纤维细胞未能在G 0/G1期积累，但没有变得不依赖血清。表达加塔-1的成纤维细胞在血清饥饿或汇合条件下表达D1、A和B1细胞周期蛋白mRNA，而这些细胞周期蛋白mRNA在相同条件下培养的亲代NIH 3 T3细胞中下调。此外，这些加塔-1表达对增殖的影响并不限于NIH 3 T3细胞，因为h加塔-1病毒感染的FDCP-1细胞（一种鼠白细胞介素-3依赖性造血细胞系）的不同克隆具有比对照细胞更慢的生长速率。基于这些数据，我们假设加塔-1在终末红细胞分化期间的细胞周期调节中起作用。(C)1996年，美国血液学会。
GATA-1, mainly expressed during erythroid differentiation, has been shown to regulate the genes specifically expressed in the late stages of erythropoiesis and to protect erythroid cells from apoptosis, suggesting that it might interfere with the cell cycle. By expressing the retrovirally transduced human GATA-1 cDNA in NIH3T3 fibroblasts, we have shown that GATA-1 alone was unable to transactivate its erythroid-specific target genes in these nonerythroid cells. However, GATA-1 expression had a dramatic effect on the proliferation of these fibroblasts. The cloning efficiency of the GATA-1-expressing fibroblasts was maintained but their S phase was greatly elongated and their G1 and G2/M phases were reduced, impairing substantially their proliferation. When cultured at low serum concentrations for 48 hours, GATA-1-expressing fibroblasts failed to accumulate in the G0/G1 phases but did not become serum independent. GATA-1-expressing fibroblasts expressed D1, A, and B1 cyclin mRNAs under conditions of serum starvation or at confluence, whereas these cyclin mRNAs were downregulated in the parental NIH3T3 cells cultured under the same conditions. Moreover, these effects of GATA-1 expression on proliferation were not limited to NIH3T3 cells, since different clones of hGATA-1 virus-infected FDCP-1 cells, a murine interleukin-3-dependent hematopoietic cell line, had a slower growth rate than control cells, Based on these data, we hypothesize that GATA-1 plays a role in the regulation of the cell cycle during terminal erythroid differentiation. (C) 1996 by The American Society of Hematology.