Caspase-mediated cleavage of the U snRNP-associated Sm-F protein during apoptosis.
Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive systemic autoimmunity in susceptible hosts. The spliceosomal Sm proteins are recognized by the so-called anti-Sm autoantibodies, an antibody population found exclusively in patients suffering from systemic lupus erythematosus. We have studied the effects of apoptosis on the Sm proteins and demonstrate that one of the Sm proteins, the Sm-F protein, is proteolytically cleaved in apoptotic cells. Cleavage of the Sm-F protein generates a 9-kDa apoptotic fragment, which remains associated with the U snRNP complexes in apoptotic cells. Sm-F cleavage is dependent on caspase activation and the cleavage site has been located near the C-terminus, EEED(81) downward arrow G. Use of different caspase inhibitors suggests that besides caspase-8 other caspases are implicated in Sm-F cleavage. A C-terminally truncated mutant of the Sm-F protein, representing the modified form of the protein, is capable of forming an Sm E-F-G complex in vitro that is recognized by many anti-Sm patient sera.
Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, University of Nijmegen, NL-6500 HB, Nijmegen, The Netherlands.
K C R
KC
Malmegrim de Farias
X
X
Saelens
G J M
GJ
Pruijn
P
P
Vandenabeele
W J
WJ
van Venrooij
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens; D015153:Blotting, Western; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D019014:fas Receptor / Q000276:immunology; D055517:snRNP Core Proteins
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D001324:Autoantigens; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D017412:Ribonucleoprotein, U1 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C526413:SNRPE protein, human; C526414:SNRPF protein, human; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor; D055517:snRNP Core Proteins; D020169:Caspases