Project PXD000216

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Biomedical Dataset
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Summary

Title

Proteome Changes Induced by Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells

Description

Inhibition of deregulated protein kinases by small molecule drugs has evolved into a major therapeutic strategy for the treatment of human malignancies. Imatinib mesylate has emerged as the leading compound to treat chronic myeloid leukemia (CML), through its inhibition of Bcr- Abl tyrosine kinases, and other cancers. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new BCR-ABL inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib showed large interest since the introduction of the nilotibin. To identify the cellular pathways affected by new synthesized compounds, we applied mass spectrometry together with stable isotope labeling by amino acids in cell culture (SILAC) for the comparative study of protein expression in K562 cells that were untreated or treated with imatinib and imatinib derivates. Further, the global proteome of the K562 cells treated with imatinib were quantitatively compared with the cells treated with the new compounds. This study enriched our knowledge about direct cellular targets of kinase selective drugs. Further the results offered important new knowledge for gaining insights into the structural effects of action of the new compounds. Samples were analyzed on a longer column (30cm) and a longer gradient (180min). Raw data files were processed with Mascot distiller 2.3. The mgf files were searched with Mascot daemon 2.3. The quantification was also done by Mascot Distiller. All data was stored in ms_lims. The manual validation of false peptide ratios was done with Rover (part of ms_lims). Fixed modifications: none. Variable modifications: acetylation of peptide N-terminus, pyroglutamate formation of N-terminal glutamine, methionine oxidation. Enzyme: trypsine with one missed cleavage allowed. Precursor mass tolerance: 10 ppm. Peptide fragment mass tolerance: 0.5 Da Quantitation method: SILAC arginine and lysine +6 Da. Overview of the 17 different analyses: B SK23 vs DMSO C Y22 vs DMSO D SK20 vs DMSO E Y18 vs DMSO I SK20 vs DMSO K Y18 vs DMSO O Y22 vs DMSO R Imatinib vs Water Z Imatinib vs Water J SK20 vs Imatinib M SK23 vs Imatinib N Y22 vs Imatinib P SK23 vs Imatinib Q Y18 vs Imatinib S Y22 vs Imatinib T SK20 vs Imatinib Y Y18 vs Imatinib

Sample Processing Protocol

Not available

Data Processing Protocol

Not available

Contact

Pieter-Jan De Bock, Biochemistry

Submission Date

18/04/2013

Publication Date

30/06/2014

Tissue

Not available

Software

Unknown

Experiment Type

Bottom-up proteomics

Assay count

17

Publication

Publication pending

Assay

Page 1 2
Page size 10
Showing 1 - 10 of 17 results
# Accession Title Proteins Peptides Unique Peptides Spectra Identified Spectra View in Reactome
1 29268 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 854 14682 3703 65130 14682
2 29269 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 855 14759 3656 64564 14759
3 29270 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 912 14376 4167 53377 14376
4 29271 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 980 14958 4345 56398 14958
5 29272 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 934 15278 4162 58970 15278
6 29273 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 846 11105 3168 50906 11105
7 29274 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 922 15410 4186 58311 15410
8 29275 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 834 11138 3199 51261 11138
9 29276 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 868 12172 3530 52426 12172
10 29277 Global Proteome Quantification of Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells 848 12456 3497 52531 12456