Department of Medicine, University of California, Los Angeles, USA.
Nucleus. 2011 Jan-Feb;2(1):4-9. doi: 10.4161/nucl.2.1.13723.
Lmna yields two major protein products in somatic cells, lamin C and prelamin A. Mature lamin A is produced from prelamin A by four posttranslational processing steps-farnesylation of a carboxyl-terminal cysteine, release of the last three amino acids of the protein, methylation of the farnesylcysteine, and the endoproteolytic release of the carboxyl-terminal 15 amino acids of the protein (including the farnesylcysteine methyl ester). Although the posttranslational processing of prelamin A has been conserved in vertebrate evolution, its physiologic significance remains unclear. Here we review recent studies in which we investigated prelamin A processing with Lmna knock-in mice that produce exclusively prelamin A (Lmna(PLAO)), mature lamin A (Lmna(LAO)) or nonfarnesylated prelamin A (Lmna(nPLAO)). We found that the synthesis of lamin C is dispensable in laboratory mice, that the direct production of mature lamin A (completely bypassing all prelamin A processing) causes no discernable pathology in mice, and that exclusive production of nonfarnesylated prelamin A leads to cardiomyopathy.
Lmna 在体细胞中产生两种主要的蛋白质产物，即 lamin C 和 prelamin A。成熟的 lamin A 由 prelamin A 通过四个翻译后加工步骤产生 - 羧基末端半胱氨酸的法尼基化、蛋白质最后三个氨基酸的释放、法尼基半胱氨酸的甲基化以及蛋白质羧基末端 15 个氨基酸的内切蛋白酶释放（包括法尼基半胱氨酸甲酯）。尽管 prelamin A 的翻译后加工在脊椎动物进化中得到了保守，但它的生理意义仍不清楚。在这里，我们回顾了最近的研究，这些研究使用专门产生 prelamin A（Lmna(PLAO)）、成熟 lamin A（Lmna(LAO)）或非法尼基化 prelamin A（Lmna(nPLAO)）的 Lmna 基因敲入小鼠来研究 prelamin A 的加工。我们发现 lamin C 的合成在实验小鼠中是可有可无的，直接产生成熟 lamin A（完全绕过所有 prelamin A 加工）在小鼠中不会引起明显的病理学变化，而专门产生非法尼基化的 prelamin A 会导致心肌病。
