Regulation of microtubule dynamics and myogenic differentiation by MURF, a striated muscle RING-finger protein.

Regulation of microtubule dynamics and myogenic differentiation by MURF, a striated muscle RING-finger protein.
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通过Murf(一种横纹肌肉手指蛋白)调节微管动力学和肌原性分化。

DOI:
10.1083/jcb.150.4.771
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发表时间:
2000-08-21
影响因子:
7.8
通讯作者:
Olson, E N
Olson, E N
中科院分区:
生物学1区
文献类型:
--
作者:
Spencer, J A;Eliazer, S;Ilaria, R L Jr;Richardson, J A;Olson, E N

文献摘要

被引文献

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环指结构域是一种新型的锌结合Cys-His蛋白基序,存在于越来越多参与信号传导、遍在蛋白化、基因转录、分化和形态发生的蛋白质中。我们描述了一种新的肌肉特异性环指蛋白(MURF),在整个出生前和出生后的小鼠发育过程中,在心脏和骨骼肌细胞中特异性表达。MURF属于环指蛋白的RING-B-box-coiled-coil亚类,其特征在于NH 2末端的环指,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的富含亮氨酸的卷曲螺旋结构域介导与微管的结合,而环指结构域是微管稳定所需的,并且同源寡聚化需要额外的区域。MURF的表达建立了一个细胞微管网络,该网络对生物碱、寒冷和钙诱导的微管解聚具有抗性。这些结果确定MURF作为横纹肌细胞微管网络的肌源性调节剂,并揭示了微管组织和肌发生之间的联系。
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 NH2-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.