[No authors listed]
14-3-3 is a family of proteins comprising several isoforms that, in many cases, promote cell survival by association with proapoptotic proteins. This study was designed to obtain further understanding of the 14-3-3 role in apoptosis regulation, by analyzing apoptosis-related protein-14-3-3 interactions. Western blot analysis of an eluted fraction from the 14-3-3-affinity chromatography column identified proapoptotic proteins as receptor-interacting protein 3 and Bcl-2-antagonist/killer as new phophorylation-dependent 14-3-3-binding proteins under physiological conditions. The apoptosis inducer C2-ceramide promoted decay of the 14-3-3-binding signal of protein cell extracts. Investigation of the role of 14-3-3 in C2-ceramide-induced apoptosis showed that depletion of the 14-3-3zeta isoform sensitized to cell death, whereas overexpression of this isoform delayed cell death. A combination of tandem affinity purification and liquid chromatography-tandem MS techniques identified 15 proteins involved in cell survival processes whose 14-3-3-binding status changed during C2-ceramide-induced apoptosis. Under physiological conditions, desmin was clearly identified as a new 14-3-3-interactor protein, and vasodilator-stimulated phosphoprotein, nucleophosmin and calmodulin, whose 14-3-3 binding was suggested by others on the basis of MS analysis, were confirmed here as phosphorylation-dependent 14-3-3-associated proteins. Interestingly, proteins related to the regulation of DNA double-strand break repair in the early stages of apoptosis, such as DNA-dependent protein kinase, or the regulation of cell shrinkage during apoptosis, such as vasodilator-stimulated phosphoprotein and death promoters like receptor-interacting protein 3, were identified as 14-3-3-associated proteins whose 14-3-3-binding status changed when apoptosis was initiated. The functional diversity of these identified proteins suggests that 14-3-3 may regulate the apoptotic process through new mechanisms, in addition to others previously characterized.
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BMH1, MYL12B, P3H4, YWHAQ, RIPK3, CEP250, HIST4H4, CPS1, DES, EEF1A1, RALY, ANKRD18A, SFN, DBNL, H1F0, HIST1H1C, HIST1H1D, HIST1H1T, H2AFX, HIST1H2BD, HMGCS2, HNRNPA2B1, HNRNPC, HSPB1, KRT8, KRT17, KRT18, LMNA, MYH2, MYH7, MYH9, MYH11, MYL3, NPM1, ATP5A1, ATP5B, BANK1, HIST2H4B, PRKDC, DIABLO, BAD, BAK1, ACTA2, ACTB, RPS3, TUT1, WNK4, STAT3, ACTG1, TPM1, TSC2, TTN, TUBB2A, VASP, VIM, YWHAB, YWHAE, YWHAG, YWHAH, YWHAZ, CACNA1S, CALM1, CALM2, CALM3, HIST1H4I, HIST1H2AI, HIST1H2AK, HIST1H2AL, HIST1H2AM, HIST1H4A, HIST1H4D, HIST1H4F, HIST1H4K, HIST1H4J, HIST1H4C, HIST1H4H, HIST1H4B, HIST1H4E, HIST1H4L, HIST2H4A, USP42, TUBA1C, MYLK2, MYH13, RIPK1, ACTN2, HIST1H2AG, TGIF2LY
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