Hollenberg S M, Cheng P F, Weintraub H
Howard Hughes Medical Institute Laboratory, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8028-32. doi: 10.1073/pnas.90.17.8028.
DNA sequences encoding the hormone-binding domains of several steroid hormone receptors were fused in frame to the MyoD gene. When the gene for this chimeric protein was expressed in NIH 3T3 or 10T1/2 fibroblasts, these cells displayed hormone-dependent induction of myogenesis. Our experiments focused on cell lines expressing estrogen receptor-MyoD chimeras. Induction of these lines in the presence of estradiol and an inhibitor of protein synthesis, cycloheximide, resulted in the activation of the endogenous myogenin gene but did not activate the muscle-specific creatine kinase or cardiac alpha-actin gene. This result suggests that MyoD is not a "direct" activator of these downstream myogenic genes but must first activate myogenin as an intermediary. Once muscle is induced by estrogen receptor-MyoD the muscle phenotype is very stable and does not need the continued presence of estradiol for its maintenance.
将编码几种类固醇激素受体激素结合结构域的DNA序列与MyoD基因读框融合。当这种嵌合蛋白的基因在NIH 3T3或10T1/2成纤维细胞中表达时，这些细胞表现出激素依赖性的肌生成诱导。我们的实验集中在表达雌激素受体-MyoD嵌合体的细胞系上。在存在雌二醇和蛋白质合成抑制剂环己酰亚胺的情况下诱导这些细胞系，导致内源性肌细胞生成素基因的激活，但未激活肌肉特异性肌酸激酶或心肌α-肌动蛋白基因。这一结果表明，MyoD不是这些下游肌源性基因的“直接”激活剂，而是必须首先激活肌细胞生成素作为中介。一旦雌激素受体-MyoD诱导出肌肉，肌肉表型就非常稳定，维持其状态不需要持续存在雌二醇。
