Ca(2+)-regulated serine protease associated with the nuclear scaffold.
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.
Clawson
G A
GA
Department of Pathology and Biological Chemistry, Pennsylvania State University, Hershey 17033.
Norbeck
L L
LL
Hatem
C L
CL
Rhodes
C
C
Amiri
P
P
McKerrow
J H
JH
Patierno
S R
SR
Fiskum
G
G
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D006224:Cricetinae; D005347:Fibroblasts / Q000187:drug effects; D007382:Intermediate Filaments / Q000378:metabolism; D034882:Lamins; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008297:Male; D008647:Mesocricetus / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015530:Nuclear Matrix / Q000201:enzymology*; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000276:immunology / Q000302:isolation & purification* / Q000502:physiology; D013045:Species Specificity; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D034882:Lamins; D009687:Nuclear Proteins; D010455:Peptides; D012697:Serine Endopeptidases; C078807:nuclear scaffold serine protease; D002118:Calcium