PXD067308

PXD067308 is an original dataset announced via ProteomeXchange.

Title	Ras-MAPK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis.
Description	In this study, we deciphered cellular mechanisms underlying AXIN1 loss by MEK1/2 inhibition in colorectal cancer (CRC). We observed that both MEK1/2 and GSK3B inhibitors strongly reduce AXIN1 levels across multiple CRC models. Inhibition of MEK1/2, but not GSK3B, causes a reduction of AXIN1 transcript levels. While GSK3B inhibition results in rapid protein degradation of AXIN1, targeting of MEK1/2 alters neither protein stability nor post-translational modifications of AXIN1. Instead, MEK1/2 inhibition represses global translation via an mTOR dependent mechanism, which is sufficient to cause AXIN1 loss. Concordantly, mTOR inhibitors phenocopy the effect of MEK1/2 inhibitors on AXIN1 levels. Our study demonstrates that AXIN1 protein homeostasis is critically controlled by Ras-MAPK signaling at the level of protein synthesis, and that its perturbation by MEK1/2 inhibitors result in AXIN1 loss.
HostingRepository	PRIDE
AnnounceDate	2026-06-03
AnnouncementXML	Submission_2026-06-03_01:37:04.606.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robert Ihnatko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-13 10:43:15	ID requested
⏵ 1	2026-06-03 01:37:05	announced

10.1186/s12964-026-02963-4;

10.1186/S12964-026-02963-4;

submitter keyword: GSK3B inhibition, MEK inhibition, HCT116,immunoprecipitation, LC-MS/MS, colorectal cancer

Dr. Jeroen Krijgsveld
contact affiliation	German Cancer Research Center (DKFZ) Heidelberg University Medical Faculty Im Neuenheimer Feld 581 69120 Heidelberg Germany
contact email	j.krijgsveld@dkfz-heidelberg.de
lab head
Robert Ihnatko
contact affiliation	German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg
contact email	robert.ihnatko@gmail.com
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/2026/06/PXD067308

PRIDE project URI

• PRIDE
  1. PXD067308
     1. Label: PRIDE project
     2. Name: Ras-MAPK inhibition induces AXIN1 loss in colorectal cancer by mTOR associated suppression of protein synthesis.