title: The 72-kDa component of signal recognition particle is cleaved during apoptosis.
abstract: Proteins cleaved by apoptotic caspases are commonly recognized by autoantibodies found in the serum of patients with rheumatic disease. We report that the 72-kDa signal recognition particle (SRP) protein, a rare target of autoantibodies found in the serum of patients with dermatomyositis and systemic lupus erythematosus, is rapidly cleaved in Jurkat T cells treated with apoptotic (i.e. Fas ligation, treatment with gamma or ultraviolet radiation, or co-culture with anisomycin or staurosporine) but not proliferative (CD3 cross-linking) stimuli. Cleavage of SRP 72 produces a 66-kDa amino-terminal fragment and a 6-kDa carboxyl-terminal fragment that is selectively phosphorylated on serine residues. Cleavage of SRP 72 is prevented by chemical and peptide caspase inhibitors, and by overexpression of bcl-2, an inhibitor of apoptotic cell death. Analysis of the carboxyl terminus of SRP 72 has identified a putative cleavage site (SELD/A) for group III caspases, and carboxyl-terminal serine residues that are highly conserved in phylogeny. Both serine phosphorylation and caspase cleavage of SRP 72 are observed in cells derived from human, dog, rat, and mouse. Canine SRP 72 is cleaved in vitro by recombinant caspase 3 but retains the ability to mediate transport of a signal peptide-containing protein into the endoplasmic reticulum lumen. The 72-kDa component of the SRP joins a growing list of autoantigens that undergo post-translational modifications during programmed cell death.
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA. pjutz@rics.bwh.harvard.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Utz
authors.forename: M
authors.initials: M
authors.lastname: Hottelet
authors.forename: T M
authors.initials: TM
authors.lastname: Le
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: M E
authors.initials: ME
authors.lastname: Geiger
authors.forename: W J
authors.initials: WJ
authors.lastname: van Venrooij
authors.forename: P
authors.initials: P
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001323:Autoantibodies; D001324:Autoantigens / Q000378:metabolism*; D061945:Caspase Inhibitors; D003882:Dermatomyositis / Q000276:immunology; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D019169:Jurkat Cells / Q000276:immunology / Q000528:radiation effects; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018271:Signal Recognition Particle / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D061945:Caspase Inhibitors; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; C503636:SRP72 protein, human; D018271:Signal Recognition Particle; C503637:Srp72 protein, mouse; D019014:fas Receptor