PXD009055

PXD009055 is an original dataset announced via ProteomeXchange.

Title	Global proteome changes of normal NIH 3T3 versus Ras-transformed NIH cells treated with 3 different Hsp90 inhibitors (geldanamycin, PU-H71 and pochoxime A)
Description	Heat shock protein 90 (Hsp90) is a major hub in the protein network that maintains cellular homeostasis and function. The qualitative and quantitative changes and rewiring of this protein network in tumor cells make them vastly dependent on Hsp90, and as a consequence its inhibition creates a profound transformation in the proteome. Here, we analyze our most recent effort that take advantage of the druggability of Hsp90 in order to understand the global changes at the proteome level that this inhibition produces. The considerable impact that the targeting of Hsp90 has on the structure of these protein networks shows that the interactome becomes laxer and presumably less efficient in communicating changes and stimuli to maintain cellular homeostasis. The lack of a systematic and proteome-wide study with genetically really comparable and matched normal and cancer cells that address the differential sensitivities to Hsp90 inhibitors, motivated us to conduct one. The transformation of NIH-3T3 cells from normal to tumoral with an oncogenic Ras mutant (Ras-T) establishes a new program of protein abundance that is efficiently targeted by Hsp90 inhibitors. Surprisingly, three different inhibitors (Geldanamycin"GA", PU-H71"PU" and Pochoxime"PX") affect a characteristic set of actors of this program. Studies like the one presented here, showing how the human proteome is changed and shaped by targeting Hsp90 could set the stage for the pharmacoproteomic profiling of responses to sets of different inhibitors and of cancer types with different molecular backgrounds. These drug-profiling analyses will be essential for the development of tailored Hsp90 inhibitors for the treatment of different tumor types and for the use in personalized medicine.
HostingRepository	jPOST
AnnounceDate	2019-02-11
AnnouncementXML	Submission_2022-09-18_03:25:34.128.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Didier Picard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ8plex reporter+balance reagent acylated N-terminal; N6-acetyl-L-lysine; iTRAQ8plex reporter+balance reagent N-acylated residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-27 06:02:13	ID requested
1	2019-02-11 06:25:08	announced
2	2021-02-04 16:43:48	announced	2021-02-04: Updated FTP location.
⏵ 3	2022-09-18 03:25:35	announced	2022-09-18: Updated FTP location.

Echeverria PC, Bhattacharya K, Joshi A, Wang T, Picard D, The sensitivity to Hsp90 inhibitors of both normal and oncogenically transformed cells is determined by the equilibrium between cellular quiescence and activity. PLoS One, 14(2):e0208287(2019) [pubmed]

submitter keyword: Hsp90, Hsp90 inhibition, Hsp90 inhibition sensitivity, quantitative proteomics, Ras-transformation, normal vs cancer, pharmacoproteomic profiling

Didier PIcard
lab head
Didier Picard
contact affiliation	UNIGE-Sciences III
dataset submitter

jPOST dataset URI

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