Spencer J A, Eliazer S, Ilaria R L, Richardson J A, Olson E N
Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9148, USA.
J Cell Biol. 2000 Aug 21;150(4):771-84. doi: 10.1083/jcb.150.4.771.
The RING-finger domain is a novel zinc-binding Cys-His protein motif found in a growing number of proteins involved in signal transduction, ubiquitination, gene transcription, differentiation, and morphogenesis. We describe a novel muscle-specific RING-finger protein (MURF) expressed specifically in cardiac and skeletal muscle cells throughout pre- and postnatal mouse development. MURF belongs to the RING-B-box-coiled-coil subclass of RING-finger proteins, characterized by an NH(2)-terminal RING-finger followed by a zinc-finger domain (B-box) and a leucine-rich coiled-coil domain. Expression of MURF is required for skeletal myoblast differentiation and myotube fusion. The leucine-rich coiled-coil domain of MURF mediates association with microtubules, whereas the RING-finger domain is required for microtubule stabilization and an additional region is required for homo-oligomerization. Expression of MURF establishes a cellular microtubule network that is resistant to microtubule depolymerization induced by alkaloids, cold and calcium. These results identify MURF as a myogenic regulator of the microtubule network of striated muscle cells and reveal a link between microtubule organization and myogenesis.
指环结构域是一种新型的锌结合半胱氨酸-组氨酸蛋白质基序，在越来越多参与信号转导、泛素化、基因转录、分化和形态发生的蛋白质中被发现。我们描述了一种新型的肌肉特异性指环蛋白（MURF），它在小鼠出生前和出生后的整个发育过程中，在心肌和骨骼肌细胞中特异性表达。MURF属于指环蛋白的RING-B-box-卷曲螺旋亚类，其特征是NH(2)端为指环结构域，随后是锌指结构域（B-box）和富含亮氨酸的卷曲螺旋结构域。MURF的表达是骨骼肌成肌细胞分化和肌管融合所必需的。MURF富含亮氨酸的卷曲螺旋结构域介导与微管的结合，而指环结构域是微管稳定所必需的，另外一个区域是同源寡聚化所必需的。MURF的表达建立了一个对生物碱、寒冷和钙诱导的微管解聚具有抗性的细胞微管网络。这些结果确定MURF是横纹肌细胞微管网络的生肌调节因子，并揭示了微管组织与肌生成之间的联系。
