Growth factor-induced delayed early response genes

Growth factor-induced delayed early response genes
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DOI:
10.1128/mcb.12.9.3919-3929.1992
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发表时间:
1992-09
影响因子:
5.3
通讯作者:
Anmhony Lanahan;John B. Williams;L. Sanders;D. Nathans;Howard Hughes
Anmhony Lanahan;John B. Williams;L. Sanders;D. Nathans;Howard Hughes
中科院分区:
生物学2区
文献类型:
--
作者:
Anmhony Lanahan;John B. Williams;L. Sanders;D. Nathans;Howard Hughes

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生长因子诱导细胞基因的顺序表达,其产物被认为是对生长因子的长期反应。在小鼠3T3成纤维细胞中,在加入血小板衍生生长因子、成纤维细胞生长因子或血清后的几分钟内,最先表达的基因(即早期基因)被激活。通过cDNA克隆,我们已经确定了在血清诱导DNA复制前几个小时和几个小时后被激活的基因。这些延迟的早期反应基因的激活需要新的蛋白质合成,可能是前面描述的即刻-早期转录因子的合成。对13个不同的延迟早期cDNA进行了部分或全部测序,约占650个初级分离株的40%,其中8个与已知基因序列有关,5个与已知基因序列无关。前者包括编码非组蛋白染色体蛋白[HMGI(Y)和HMGI-C]的cDNA,与人巨噬细胞移动抑制因子(MIF)相关的腺嘌呤磷酸核糖基转移酶(APRT),与人红细胞整体膜蛋白同源的主要内在蛋白(MIP)家族的蛋白质,以及细胞周期蛋白Cyclin。在3T3细胞中,对生长因子的延迟早期基因反应似乎至少与前面描述的即时早期基因反应一样复杂。
Growth factors induce the sequential expression of cellular genes whose products are thought to mediate long-term responses to the growth factors. In mouse 3T3 fibroblastic cells, the first genes to be expressed (immediate-early genes) are activated within minutes after the addition of platelet-derived growth factor, fibroblast growth factor, or serum. By cDNA cloning, we have identified genes that are activated after a delay of a few hours and several hours prior to serum-induced DNA replication. Activation of these delayed early response genes requires new protein synthesis, presumably the synthesis of immediate-early transcription factors described previously. Partial or complete sequencing of 13 different delayed early cDNAs, representing about 40% of the 650 primary cDNA isolates, revealed that 8 were related to known gene sequences and 5 were not. Among the former are cDNAs encoding nonhistone chromosomal proteins [HMGI(Y) and HMGI-C], adenine phosphoribosyltransferase (APRT), a protein related to human macrophage migration inhibitory factor (MIF), a protein of the major intrinsic protein (MIP) family homologous to the integral membrane protein of human erythrocytes, and cyclin CYL1. In 3T3 cells, the delayed early gene response to growth factors appears to be at least as complex as the immediate-early gene response previously described.