Maske Christopher P, Hollinshead Michael S, Higbee Niall C, Bergo Martin O, Young Stephen G, Vaux David J
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
J Cell Biol. 2003 Sep 29;162(7):1223-32. doi: 10.1083/jcb.200303113. Epub 2003 Sep 22.
The mammalian nuclear lamina protein lamin B1 is posttranslationally modified by farnesylation, endoproteolysis, and carboxymethylation at a carboxyl-terminal CAAX motif. In this work, we demonstrate that the CAAX endoprotease Rce1 is required for lamin B1 endoproteolysis, demonstrate an independent pool of proteolyzed but nonmethylated lamin B1, as well as fully processed lamin B1, in interphase nuclei, and show a role for methylation in the organization of lamin B1 into domains of the nuclear lamina. Deficiency in the endoproteolysis or methylation of lamin B1 results in loss of integrity and deformity of the nuclear lamina. These data show that the organization of the nuclear envelope and lamina is dependent on a mechanism involving the methylation of lamin B1, and they identify a potential mechanism of laminopathy involving a B-type lamin.
哺乳动物核纤层蛋白核纤层蛋白B1在羧基末端CAAX基序处进行法尼基化、内切蛋白水解和羧甲基化的翻译后修饰。在这项研究中，我们证明了CAAX内切蛋白酶Rce1是核纤层蛋白B1内切蛋白水解所必需的，在间期细胞核中展示了一个独立的已被蛋白水解但未甲基化的核纤层蛋白B1池以及完全加工的核纤层蛋白B1，并表明甲基化在核纤层蛋白B1组织成核纤层结构域中发挥作用。核纤层蛋白B1的内切蛋白水解或甲基化缺陷会导致核纤层完整性丧失和畸形。这些数据表明核膜和核纤层的组织依赖于一种涉及核纤层蛋白B1甲基化的机制，并且它们确定了一种涉及B型核纤层蛋白的核纤层病潜在机制。
