PXD032942

PXD032942 is an original dataset announced via ProteomeXchange.

Title	Thermal Proteome Profiling Datasets for smarTPCA
Description	Chemical biology and the application of small molecules has proven to be a potent perturbation strategy especially for the functional elucidation of proteins, their networks and regulators. In recent years, the cellular thermal shift assay (CETSA) and its proteome-wide extension, thermal proteome profiling (TPP), have proven to be effective tools for identifying interactions of small molecules with their target proteins as well as off-targets in living cells. Here, we asked the question if isothermal dose-response (ITDR) CETSA can be exploited to characterize secondary effects downstream of the primary binding event, such as changes in post-translational modifications or protein-protein interactions (PPI). Applying ITDR-CETSA to MAPK14 kinase inhibitor treatment of living HL-60 cells, we found similar dose-responses for the direct inhibitor target and its known interaction partners MAPKAPK2 and MAPKAPK3. Extension of the dose-response similarity comparison to the proteome wide level using TPP with compound concentration range (TPP-CCR) revealed not only the known MAPK14 interaction partners MAPKAPK2 and MAPKAPK3, but also the potentially new intracellular interaction partner MYLK. We are confident that dose-dependent small molecule treatment in combination with ITDR-CETSA or TPP-CCR similarity assessment will not only allow discrimination between primary and secondary effects, but also provide a novel method to study PPI in living cells without perturbation by protein modification, which we named "small molecule arranged thermal proximity coaggregation" (smarTPCA).
HostingRepository	PRIDE
AnnounceDate	2022-06-09
AnnouncementXML	Submission_2022-06-09_14:40:58.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Lenz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-02 14:01:35	ID requested
⏵ 1	2022-06-09 14:40:59	announced

Lenz T, St, ü, hler K, ggregation (smarTPCA)-A Novel Approach to Characterize Protein-Protein Interactions in Living Cells by Similar Isothermal Dose-Responses. Int J Mol Sci, 23(10):(2022) [pubmed]

submitter keyword: HL-60 cell line, kinase inhibitors, thermal proteome profiling (TPP), TPP with temperature range (TPP-TR) or compound concentration range (TPP-CCR), small molecule arranged thermal proximity coaggregation (smarTPCA)

Kai Stühler
contact affiliation	1 Molecular Proteomics Laboratory, Biological Medical Research Center, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany 2 Institute for Molecular Medicine, Proteome Research, University Hospital and Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
contact email	kai.stuehler@hhu.de
lab head
Thomas Lenz
contact affiliation	MPL/BMFZ, HHU Düsseldorf
contact email	thomas.lenz@hhu.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/06/PXD032942

PRIDE project URI

• PRIDE
  1. PXD032942
     1. Label: PRIDE project
     2. Name: Thermal Proteome Profiling Datasets for smarTPCA