title: Proteome analysis of nuclear matrix proteins during apoptotic chromatin condensation.
abstract: The nuclear matrix (NM) is considered a proteinaceous scaffold spatially organizing the interphase nucleus, the integrity of which is affected during apoptosis. Caspase-mediated degradation of NM proteins, such as nuclear lamins, precedes apoptotic chromatin condensation (ACC). Nevertheless, other NM proteins remain unaffected, which most likely maintain a remaining nuclear structure devoid of chromatin. We, therefore, screened various types of apoptotic cells for changes of the nuclear matrix proteome during the process of apoptotic ACC. Expectedly, we observed fundamental alterations of known chromatin-associated proteins, comprising both degradation and translocation to the cytosol. Importantly, a consistent set of abundant NM proteins, some (e.g. hNMP 200) of which displaying structural features, remained unaffected during apoptosis and might therefore represent constituents of an elementary scaffold. In addition, proteins involved in DNA replication and DNA repair were found accumulated in the NM fraction before cells became irreversibly committed to ACC, a time point characterized in detail by inhibitor studies with orthovanadate. In general, protein alterations of a consistent set of NM proteins (67 of which were identified), were reproducibly detectable in Fas-induced Jurkat cells, in UV-light treated U937 cells and also in staurosporine-treated HeLa cells. Our data indicate that substantial alterations of proteins linking chromatin to an elementary nuclear protein scaffold might play an intriguing role for the process of ACC.
authors.affiliation: Institute of Cancer Research, University of Vienna, A-1090 Vienna, Austria. Christopher.Gerner@univie.ac.at
authors.forename: C
authors.initials: C
authors.lastname: Gerner
authors.forename: J
authors.initials: J
authors.lastname: Gotzmann
authors.forename: U
authors.initials: U
authors.lastname: Fröhwein
authors.forename: C
authors.initials: C
authors.lastname: Schamberger
authors.forename: A
authors.initials: A
authors.lastname: Ellinger
authors.forename: G
authors.initials: G
authors.lastname: Sauermann
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002843:Chromatin / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004260:DNA Repair; D004261:DNA Replication; D015180:Electrophoresis, Gel, Two-Dimensional; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D020543:Proteome / Q000502:physiology*; D014638:Vanadates / Q000494:pharmacology; D019014:fas Receptor / Q000502:physiology
chemical_list: D002843:Chromatin; D034521:Nuclear Matrix-Associated Proteins; D020543:Proteome; D019014:fas Receptor; D014638:Vanadates