Clawson G A, Norbeck L L, Hatem C L, Rhodes C, Amiri P, McKerrow J H, Patierno S R, Fiskum G
Department of Pathology and Biological Chemistry, Pennsylvania State University, Hershey 17033.
Cell Growth Differ. 1992 Nov;3(11):827-38.
The nuclear scaffold (NS) is a proteinaceous network of orthogonally arrayed intermediate filament proteins, termed lamins, which is responsible for nuclear structure. Recent work has demonstrated that a subset of lamins A/C is proteolytically cleaved to produce an ATP-binding protein. This proteolytic cleavage is accomplished by a NS protease activity, which shows a considerable selectivity for lamins A/C and is stringently regulated by Ca2+ in vitro, suggesting that it might also participate in control of NS breakdown in various scenarios. Here, we identify the major NS protease as a novel serine protease with a predominantly chymotryptic-like substrate preference, and we show that even transient perturbations in cytosolic Ca2+ have significant effects on the NS protease activity. This NS protease activity shows extensive similarities to the multicatalytic proteinase complex. In addition to a potential role in control of NS breakdown at mitosis and/or under pathological conditions, this NS protease is also strategically located for other functions, such as inactivation of various oncogenic proteins or maturation-promoting factor.
核支架（NS）是由正交排列的中间丝蛋白（称为核纤层蛋白）构成的蛋白质网络，负责维持细胞核结构。最近的研究表明，核纤层蛋白A/C的一个亚群会被蛋白水解切割，产生一种ATP结合蛋白。这种蛋白水解切割是由NS蛋白酶活性完成的，该活性对核纤层蛋白A/C具有相当高的选择性，并且在体外受到Ca2+的严格调控，这表明它可能也参与了在各种情况下对NS解体的控制。在这里，我们确定主要的NS蛋白酶是一种新型丝氨酸蛋白酶，其底物偏好主要类似于胰凝乳蛋白酶，并且我们发现即使是胞质Ca2+的短暂扰动也会对NS蛋白酶活性产生显著影响。这种NS蛋白酶活性与多催化蛋白酶复合体有广泛的相似性。除了在有丝分裂和/或病理条件下控制NS解体方面可能发挥的作用外，这种NS蛋白酶在其他功能方面也具有战略定位，例如使各种致癌蛋白或促成熟因子失活。
