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

Cell Growth Differ. 1992 Nov;3(11):827-38.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / physiology*
  • Calmodulin / physiology
  • Cricetinae
  • Fibroblasts / drug effects
  • Intermediate Filaments / metabolism
  • Lamins
  • Liver / enzymology
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mesocricetus / metabolism
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Molecular Weight
  • Nuclear Matrix / enzymology*
  • Nuclear Proteins / metabolism
  • Peptides / pharmacology
  • Rats
  • Rats, Sprague-Dawley / metabolism
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / isolation & purification*
  • Serine Endopeptidases / physiology
  • Species Specificity
  • Substrate Specificity
  • Tumor Cells, Cultured

Substances

  • Calmodulin
  • Lamins
  • Nuclear Proteins
  • Peptides
  • Serine Endopeptidases
  • nuclear scaffold serine protease
  • Calcium