Dias P, Dilling M, Houghton P
Department of Molecular Pharmacology, St Jude Children's Research Hospital, Memphis, TN 38101.
Semin Diagn Pathol. 1994 Feb;11(1):3-14.
In recent years, significant advances have been made in understanding the molecular mechanisms involved in the regulation of skeletal-muscle differentiation. This review focuses on the role of the MyoD family of myogenic transcription factors that includes MyoD, myf-5, myogenin, and MRF4 (herculin or myf-6) in myogenesis. Members of this family share sequence homology for the basic-helix-loop-helix (bHLH) regulatory motif. The basic domain is required for DNA binding, whereas the HLH domain is required for dimerization. The bHLH motif confers both properties of transcriptional activation of muscle specific genes and inhibition of cell growth through collaboration with the E2A gene products (E12 and E47) and the retinoblastoma gene product (pRB). The functions of the MyoD family can be suppressed through inhibition of their expression or activity by various factors. These include peptide growth factors (FGF and TGF-beta), immediate early gene products (Fos, Jun and Myc), other oncogene products (Ras, Src), the Id protein, and innervation. The use of gene-knockout animal models has shown that there is some degree of functional redundancy in that inactivation of either MyoD or myf-5 has no effect on muscle development, whereas inactivation of both genes results in an absolute lack of muscle cells. In contrast, the inactivation of myogenin alone results in mice with gross deficiency of mature muscle.
近年来，在理解骨骼肌分化调控所涉及的分子机制方面取得了重大进展。本综述聚焦于肌源性转录因子MyoD家族的作用，该家族包括MyoD、myf-5、肌细胞生成素和MRF4（赫库林或myf-6）在肌生成中的作用。这个家族的成员在基本螺旋-环-螺旋（bHLH）调控基序上具有序列同源性。基本结构域是DNA结合所必需的，而HLH结构域是二聚化所必需的。bHLH基序通过与E2A基因产物（E12和E47）和成视网膜细胞瘤基因产物（pRB）协同作用，赋予肌肉特异性基因转录激活和抑制细胞生长的特性。MyoD家族的功能可通过各种因素抑制其表达或活性来实现。这些因素包括肽生长因子（FGF和TGF-β）、即刻早期基因产物（Fos、Jun和Myc）、其他癌基因产物（Ras、Src）、Id蛋白和神经支配。基因敲除动物模型的研究表明，MyoD或myf-5的失活对肌肉发育没有影响，而两个基因都失活则会导致肌肉细胞完全缺失，这说明在一定程度上存在功能冗余。相比之下，单独失活肌细胞生成素会导致小鼠成熟肌肉严重缺乏。
