PXD037575

PXD037575 is an original dataset announced via ProteomeXchange.

Title	Investigation of cellular response to the HSP90 inhibition in human cells through thermal proteome profiling
Description	Heat shock proteins are responsible for protein folding in cells. HSP90 is one of the most important chaperones in human cells, and inhibiting HSP90 is a potential strategy for cancer therapy. Multiple HSP90 inhibitors have been in clinical trials. However, none of them has been approved for disease treatment due to unexpected cellular toxicity. Hence, a more comprehensive investigation of cellular responses to HSP90 inhibitors can aid in a better understanding of the molecular mechanisms of the cytotoxicity and side effects of these inhibitors. Protein thermal stability shift, which represents protein structure and interaction alterations, can provide another level of information complementary to commonly used abundance-based proteomics analysis. In this work, we systematically investigated cell responses to different HSP90 inhibitors through global quantification of protein thermal stability changes using thermal proteome profiling, together with quantification of protein abundance changes. Besides the targets and potential off-targets of the drugs, proteins with significant thermal stability changes under the HSP90 inhibition are found to be related to cell stress responses and the translation process. Moreover, proteins with thermal stability shifts under the inhibition are upstream of those with altered expressions. Importantly, the current results indicate that the inhibition of HSP90 results in a strong perturbance of cell transcription and translation processes. This study provides a different perspective to achieve a better understanding of cellular response to chaperone inhibition.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:37.708.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037575
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kejun Yin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-19 03:12:33	ID requested
1	2023-05-10 12:51:40	announced
⏵ 2	2023-11-14 09:00:38	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: heat shock protein 90, HSP90 inhibitors, and protein abundance change,Thermal proteome profiling, cell response, protein thermal stability shift

Ronghu Wu
contact affiliation	Department of Chemistry and Biochemistry, Georgia Institute of Technology, GA, US
contact email	ronghu.wu@chemistry.gatech.edu
lab head
Kejun Yin
contact affiliation	Georgia Institute of Technology
contact email	kyin49@gatech.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037575
     1. Label: PRIDE project
     2. Name: Investigation of cellular response to the HSP90 inhibition in human cells through thermal proteome profiling