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Proteome changes induced by c-myb silencing in human chronic myeloid leukemia cells suggest molecular mechanisms and putative biomarkers of hematopoietic malignancies

TitleProteome changes induced by c-myb silencing in human chronic myeloid leukemia cells suggest molecular mechanisms and putative biomarkers of hematopoietic malignancies
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2014
AuthorsDi Carli, M., Tanno Barbara, Capodicasa Cristina, Villani Maria Elena, Salzano A.M., Scaloni A., Raschellà G., Benvenuto Eugenio, and Donini Marcello
JournalJournal of Proteomics
Keywords2D-DIGE, alpha enolase, alternative RNA splicing, article, BCR-ABL Positive, Biological, biological marker, C-Myb, Cell biology, chaperonin 60, chaperonin containing TCP1, chromatin, Chronic, Chronic myeloid leukemia, controlled study, disease course, down regulation, electrospray mass spectrometry, elongation factor 2, energy metabolism, energy yield, G0 Phase, Gene expression, gene silencing, Genetic, gluconeogenesis, glucose regulated protein, glyceraldehyde 3 phosphate dehydrogenase, glycolysis, heat shock protein 70, human, human cell, Humans, K562 Cells, Leukemia, leukemia cell, mitochondrial 39 s ribosomal protein l 12, Myelogenous, Oxidative stress, phosphoglycerate mutase, phosphoglycerate mutase 1, pleiotropy, priority journal, prostaglandin E synthase, prostaglandin e synthase 2, protein analysis, Protein Biosynthesis, protein c Myb, protein disulfide isomerase, protein disulfide isomerase A3, Protein Folding, protein function, protein synthesis, proteome, Proto-Oncogene Proteins c-myb, reverse transcription polymerase chain reaction, ribosomal protein L1, RNA Interference, stress, Transcription, transcription regulation, transcriptome, triosephosphate isomerase, Tumor Markers, two dimensional difference gel electrophoresis, ubiquitination, unclassified drug

To shed light on the molecular mechanisms associated with aberrant accumulation of c-Myb in chronic myeloid leukemia, comparative proteomic analysis was performed on c-myb RNAi-specifically silenced K562 cells, sampled on a time-course basis. 2D-DIGE technology highlighted 37 differentially-represented proteins that were further characterized by nLC-ESI-LIT-MS/MS and validated by western blotting and qRT-PCR analysis. Most of the deregulated proteins were related to protein folding, energy/primary metabolism, transcription/translation regulation and oxidative stress response. Protein network analysis suggested that glycolysis, gluconeogenesis and protein ubiquitination biosynthesis pathways were highly represented, confirming also the pivotal role of c-Myc. A specific reduced representation was observed for glyceraldehyde-3-phosphate-dehydrogenase and α-enolase, suggesting a possible role of c-Myb in the activation of aerobic glycolysis. A reduced amount was also observed for stress responsive heat shock 70kDa protein and 78kDa glucose-regulated protein, previously identified as direct targets of c-Myb. Among over-represented proteins, worth mentioning is the chromatin modifier chromobox protein homolog 3 that contributes to silencing of E2F- and Myc-responsive genes in quiescent G0 cells. Data here presented, while providing novel insights onto the molecular mechanisms underlying c-Myb activity, indicate potential protein biomarkers for monitoring the progression of chronic myeloid leukemia.© 2013 Elsevier B.V.


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Citation KeyDiCarli2014200