Apoptosis consists of highly regulated pathways involving post-translational modifications and cleavage of proteins leading tosequential inactivation of the main cellular processes. Here, we focused on the apoptotic processing of one of the essentialcomponents of the mRNA splicing machinery, the U1-70K snRNP protein. We found that at an early stage of apoptosis, before thecleavage of the C-terminal part of the protein by caspase-3, the basal phosphorylation of the Ser140 residue located within theRNA recognition motif, increases very significantly. A caspase-dependent, PP1-mediated dephosphorylation of other serineresidues takes place in a subset of U1-70K proteins. The U1-70K protein phosphorylated at Ser140 is clustered in heterogeneousectopic RNP-derived structures, which are finally extruded in apoptotic bodies. The elaborate processing of the spliceosomalU1-70K protein we identified might play an important role in the regulated breakdown of the mRNA splicing machinery duringearly apoptosis. In addition, these specific changes in the phosphorylation/dephosphorylation balance and the subcellularlocalization of the U1-70K protein might explain why the region encompassing the Ser140 residue becomes a central autoantigenduring the autoimmune disease systemic lupus erythematosus.

Apoptosis-linked changes in the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K.

Cisterna, Barbara;
2008-01-01

Abstract

Apoptosis consists of highly regulated pathways involving post-translational modifications and cleavage of proteins leading tosequential inactivation of the main cellular processes. Here, we focused on the apoptotic processing of one of the essentialcomponents of the mRNA splicing machinery, the U1-70K snRNP protein. We found that at an early stage of apoptosis, before thecleavage of the C-terminal part of the protein by caspase-3, the basal phosphorylation of the Ser140 residue located within theRNA recognition motif, increases very significantly. A caspase-dependent, PP1-mediated dephosphorylation of other serineresidues takes place in a subset of U1-70K proteins. The U1-70K protein phosphorylated at Ser140 is clustered in heterogeneousectopic RNP-derived structures, which are finally extruded in apoptotic bodies. The elaborate processing of the spliceosomalU1-70K protein we identified might play an important role in the regulated breakdown of the mRNA splicing machinery duringearly apoptosis. In addition, these specific changes in the phosphorylation/dephosphorylation balance and the subcellularlocalization of the U1-70K protein might explain why the region encompassing the Ser140 residue becomes a central autoantigenduring the autoimmune disease systemic lupus erythematosus.
2008
Apoptosis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/783783
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