a Light Imaging Section, Office of Science and Technology , National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda.
b Molecular Medicine Section, Department of Molecular and Developmental Medicine , University of Siena , Siena , Italy.
Expert Opin Ther Targets. 2017 Sep;21(9):897-910. doi: 10.1080/14728222.2017.1361931. Epub 2017 Aug 4.
Obscurin, a giant protein of striated muscles, is emerging as an important player in a wide range of processes including myofibril assembly and maintenance, muscle protein degradation and intracellular signaling. Accordingly, obscurin participates to the mechanisms by which muscles adapt to physiological requirements or to pathological cues associated with cardiac and skeletal muscle diseases. Areas covered: The structure of the different obscurin isoforms identified so far, their tissue distribution and the most recent findings on obscurin in invertebrates and mammals will be reviewed. We will provide a synopsis of known molecular interactions between obscurin and other proteins and the biological relevance of these interactions for striated muscle function. The involvement of obscurin in protein degradation mechanisms and intracellular signaling will be also discussed along with initial evidence of a role of obscurin in the pathophysiology of human diseases. Expert opinion: Although still much remains to be discovered about the role of obscurin either as a structural component of the sarcomere or as a mediator of signaling pathways within muscle cells, it can be envisioned that this protein represents an interesting novel pharmacological target for the prevention and treatment of cardiac and skeletal muscle diseases.
obscurin 是一种横纹肌的巨大蛋白,作为一个重要的参与者,它在包括肌原纤维组装和维持、肌肉蛋白降解和细胞内信号转导在内的广泛过程中发挥作用。因此, obscurin 参与了肌肉适应生理需求或与心脏和骨骼肌疾病相关的病理信号的机制。 涵盖领域:本文综述了迄今为止鉴定的不同 obscurin 异构体的结构、它们的组织分布以及无脊椎动物和哺乳动物中 obscurin 的最新发现。我们将概述 obscurin 与其他蛋白质之间已知的分子相互作用以及这些相互作用对横纹肌功能的生物学意义。还将讨论 obscurin 在蛋白降解机制和细胞内信号转导中的作用,以及 obscurin 在人类疾病病理生理学中的作用的初步证据。 专家意见:尽管 obscurin 在作为肌节的结构成分或作为肌肉细胞内信号通路的介质方面的作用仍有许多有待发现,但可以想象,这种蛋白质代表了预防和治疗心脏和骨骼肌疾病的一个有趣的新型药理学靶点。