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Hypophosphorylation of the architectural chromatin protein DEK in death‐receptor‐induced apoptosis revealed by the isotope coded protein label proteomic platform
Author(s) -
Tabbert Anja,
Kappes Ferdinand,
Knippers Rolf,
Kellermann Josef,
Lottspeich Friedrich,
FerrandoMay Elisa
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200600197
Subject(s) - apoptosis , chromatin , microbiology and biotechnology , proteome , biology , inhibitor of apoptosis domain , nuclear protein , proteomics , cytoplasm , cell nucleus , crosstalk , programmed cell death , caspase , biochemistry , dna , transcription factor , gene , physics , optics
During apoptosis nuclear morphology changes dramatically due to alterations of chromatin architecture and cleavage of structural nuclear proteins. To characterize early events in apoptotic nuclear dismantling we have performed a proteomic study of apoptotic nuclei. To this end we have combined a cell‐free apoptosis system with a proteomic platform based on the differential isotopic labeling of primary amines with N ‐nicotinoyloxy‐succinimide. We exploited the ability of this system to produce nuclei arrested at different stages of apoptosis to analyze proteome alterations which occur prior to or at a low level of caspase activation. We show that the majority of proteins affected at the onset of apoptosis are involved in chromatin architecture and RNA metabolism. Among them is DEK, an architectural chromatin protein which is linked to autoimmune disorders. The proteomic analysis points to the occurrence of multiple PTMs in early apoptotic nuclei. This is confirmed by showing that the level of phosphorylation of DEK is decreased following apoptosis induction. These results suggest the unexpected existence of an early crosstalk between cytoplasm and nucleus during apoptosis. They further establish a previously unrecognized link between DEK and cell death, which will prove useful in the elucidation of the physiological function of this protein.