Identification of a novel muscle A-type lamin-interacting protein (MLIP).
Identification of a novel muscle A-type lamin-interacting protein (MLIP).
复制标题
DOI：
10.1074/jbc.m110.165548
复制
发表时间：
2011-06-03
期刊：
影响因子：
--
通讯作者：
Burgon PG
中科院分区：
文献类型：
--
作者：
Ahmady E;Deeke SA;Rabaa S;Kouri L;Kenney L;Stewart AF;Burgon PG
A型核纤层蛋白（LMNA）基因突变与年龄相关的间充质组织退行性疾病有关，如扩张型心肌病、Emery-Dreifuss肌营养不良和肢带型肌营养不良。将LMNA突变与不同人类疾病联系起来的分子机制知之甚少。在这里，我们报告了一种富含肌肉的A型纤层相互作用蛋白MLIP（C6 orf 142和2310046 A06 rik）的鉴定，这是一种独特的单拷贝基因，是爬行动物（爬行动物，鸟类和哺乳动物）的创新。MLIP编码可变剪接变体（23-57 kDa），并具有在其他蛋白质中未发现的几个新的结构基序。MLIP在心脏、骨骼肌和平滑肌中广泛表达且最丰富。MLIP与核被膜中的核纤层蛋白A和核纤层蛋白C直接相互作用并共定位。MLIP还与细胞核内的早幼粒细胞白血病（PML）体共定位。与MLIP一样，PML仅在黑猩猩中发现，这表明核被膜和PML体之间可能通过MLIP存在功能联系。通过shRNA下调核纤层蛋白A/C的表达，导致MLIP的上调和错误定位。鉴于MLIP在横纹肌和平滑肌中表达最高，它可能有助于层粘连蛋白病的间充质表型。
Mutations in the A-type lamin (LMNA) gene are associated with age-associated degenerative disorders of mesenchymal tissues, such as dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and limb-girdle muscular dystrophy. The molecular mechanisms that connect mutations in LMNA with different human diseases are poorly understood. Here, we report the identification of a Muscle-enriched A-type Lamin-interacting Protein, MLIP (C6orf142 and 2310046A06rik), a unique single copy gene that is an innovation of amniotes (reptiles, birds, and mammals). MLIP encodes alternatively spliced variants (23–57 kDa) and possesses several novel structural motifs not found in other proteins. MLIP is expressed ubiquitously and most abundantly in heart, skeletal, and smooth muscle. MLIP interacts directly and co-localizes with lamin A and C in the nuclear envelope. MLIP also co-localizes with promyelocytic leukemia (PML) bodies within the nucleus. PML, like MLIP, is only found in amniotes, suggesting that a functional link between the nuclear envelope and PML bodies may exist through MLIP. Down-regulation of lamin A/C expression by shRNA results in the up-regulation and mislocalization of MLIP. Given that MLIP is expressed most highly in striated and smooth muscle, it is likely to contribute to the mesenchymal phenotypes of laminopathies.