Cell Growth & Differentiation, Vol 3, Issue 11 827-838, Copyright © 1992 by American Association of Cancer Research

ARTICLES

Ca(2+)-regulated serine protease associated with the nuclear scaffold

GA Clawson, LL Norbeck, CL Hatem, C Rhodes, P Amiri, JH McKerrow, SR Patierno and G Fiskum
Department of Pathology and Biological Chemistry, Pennsylvania State University, Hershey 17033.

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.

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