PXD000216

PXD000216 is an original dataset announced via ProteomeXchange.

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
HostingRepository	PRIDE
AnnounceDate	2014-12-02
AnnouncementXML	Submission_2014-12-02_00:30:27.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD000216
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pieter-Jan De Bock
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	2-pyrrolidone-5-carboxylic acid (Gln): -17.026549; monohydroxylated residue: 15.994915; 6x(13)C labeled residue: 6.020129; N-acetylated residue: 42.010565
Instrument	LTQ Orbitrap; instrument model: LTQ-Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2013-04-18 04:44:01	ID requested
1	2014-06-30 08:18:25	announced
2	2014-07-28 00:34:49	announced	Updated project metadata.
⏵ 3	2014-12-02 00:30:28	announced	Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: Human, SILAC, K562, long columns, LC-MSMS, imatinib

Pieter-Jan De Bock
contact affiliation	Biochemistry
contact email	pieter-jan.debock@cea.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD000216
     1. Label: PRIDE project
     2. Name: Proteome Changes Induced by Imatinib and Novel Imatinib Derivatives in K562 Human Chronic Myeloid Leukemia Cells