Molecular Cloning of CSF-1 Receptor from Rat Myoblasts. Sequence Analysis and Regulation During Myogenesis
Molecular Cloning of CSF-1 Receptor from Rat Myoblasts. Sequence Analysis and Regulation During Myogenesis
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DOI：
10.3109/08977199209021534
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发表时间：
1992-01-01
期刊：
影响因子：
1.8
通讯作者：
Leibovitch, Serge Alexandre
中科院分区：
文献类型：
--
作者：
Borycki, Anne-Gaelle;Guillier, Martine;Leibovitch, Serge Alexandre
我们从增殖的L6α1成肌细胞中分离并测序了一个编码大鼠c-FMS基因(CSF-1受体)的基因(Mrfms)。预测的氨基酸序列与单核细胞和巨噬细胞中发现的c-fms蛋白高度一致(分别与小鼠、猫和人的c-fms蛋白有98、76和84%的同源性)。研究了在肌发生过程中调节mrfms基因表达的机制。在L6α1成肌细胞增殖过程中观察到mRfms产物，在分化过程中表达下调。连续转录分析表明，mrfms基因只在未分化的成肌细胞中转录活性。这些发现表明，L6α1成肌细胞中mrfms的水平受转录机制的控制。Mrfms转录本的半衰期至少为5小时，而环己亚胺(CHX)抑制蛋白质合成的半衰期缩短至30min，而mrfms基因的转录速率没有变化。此外，v-FMS对L6α1成肌细胞的致癌转化诱导了mrfms mRNAs的结构性上调，核连续分析表明mrfms的转录不依赖于生长因子。此外，这些发现和以前发表的其他发现表明，mrfms基因产物可能在肌肉细胞的正常和肿瘤生长中发挥作用。
We have isolated and sequenced a cDNA (mrfms) encoding rat c-fms gene (CSF-1 receptor) from proliferating L6 alpha 1 myoblasts. The predicted amino acid sequence was highly identical with the c-fms protein found in monocytes and macrophages (98,76 and 84% identity from mouse, cat and human c-fms proteins, respectively). The mechanisms responsible for the regulation of mrfms gene expression during myogenesis were examined. Mrfms products were observed during proliferation of L6 alpha 1 myoblasts and were downregulated during differentiation. Run-on transcription assays demonstrated that the mrfms gene was transcriptionally active only in undifferentiated myoblasts. These findings suggested that mrfms levels in L6 alpha 1 myoblasts are controlled by transcriptional mechanisms. The half-life of mrfms transcripts was found to be at least 5 hr while inhibition of protein synthesis with cycloheximide (CHX) decreased this half-life to 30 min without changes in the rate of mrfms gene transcription. In addition oncogenic transformation of L6 alpha 1 myoblasts by the v-fms induced constitutive upregulation of mrfms mRNAs, and nuclear run-on assays demonstrated that mrfms transcription was not growth-factor dependent. Furthermore, these findings with others previously published indicate that mrfms gene products may play a role in the normal and neoplastic growth of muscular cells.