Apoptosis-linked changes in the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K.
Apoptosis consists of highly regulated pathways involving post-translational modifications and cleavage of proteins leading to sequential inactivation of the main cellular processes. Here, we focused on the apoptotic processing of one of the essential components of the mRNA splicing machinery, the U1-70K snRNP protein. We found that at an early stage of apoptosis, before the cleavage of the C-terminal part of the protein by caspase-3, the basal phosphorylation of the Ser140 residue located within the RNA recognition motif, increases very significantly. A caspase-dependent, PP1-mediated dephosphorylation of other serine residues takes place in a subset of U1-70K proteins. The U1-70K protein phosphorylated at Ser140 is clustered in heterogeneous ectopic RNP-derived structures, which are finally extruded in apoptotic bodies. The elaborate processing of the spliceosomal U1-70K protein we identified might play an important role in the regulated breakdown of the mRNA splicing machinery during early apoptosis. In addition, these specific changes in the phosphorylation/dephosphorylation balance and the subcellular localization of the U1-70K protein might explain why the region encompassing the Ser140 residue becomes a central autoantigen during the autoimmune disease systemic lupus erythematosus.
Dieker
J
J
Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
Cisterna
B
B
Monneaux
F
F
Decossas
M
M
van der Vlag
J
J
Biggiogera
M
M
Muller
S
S
D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000378:metabolism*; D015551:Autoimmunity; D053148:Caspase 3 / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology; D021381:Protein Transport; D012326:RNA Splicing; D011994:Recombinant Proteins / Q000378:metabolism; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D017381:Spliceosomes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D001324:Autoantigens; D002843:Chromatin; D011994:Recombinant Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C490688:SNRNP70 protein, human; D012694:Serine; D054645:Protein Phosphatase 1; C505407:CASP3 protein, human; D053148:Caspase 3