PXD058235-1

PXD058235 is an original dataset announced via ProteomeXchange.

Title	CRKL enhances YAP signaling through binding and JNK/JUN pathway activation in liver cancer
Description	Hepatocellular carcinoma (HCC) presents a major health issue due to its rising incidence and limited therapeutic options. The Hippo pathway transducers yes-associated protein (YAP) and WW-domain containing transcription regulator 1 (WWTR1/TAZ) are key regulators of liver tu-morigenesis promoting tumor formation and progression. Although first inhibitors are in clinical trials, targeting the upstream activation of YAP/TAZ could prove equally beneficial. To identify regulators of YAP/TAZ activity, we carried out a proximity labelling approach (BioID) coupled to mass-spectrometry. We verified CRKL as a new YAP-exclusive interaction partner, which is overexpressed in HCC patients correlating with YAP expression and activity as well as poor survival prognosis. In vitro experiments demonstrated CRKL dependent cell survival and loss of YAP binding induced through actin disruption. Moreover, we delineated an activation of the JNK/JUN pathway by CRKL, which promoted YAP transcription. Our data thus illustrated that CRKL not only promoted YAP activity through its binding but also through the induction of YAP transcription by JNK/JUN activation. This highlights the JNK/JUN pathway as a possible target to abrogate YAP expression in HCC patients.
HostingRepository	PRIDE
AnnounceDate	2024-11-26
AnnouncementXML	Submission_2024-11-26_05:25:50.071.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcin Luzarowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-25 07:10:21	ID requested
⏵ 1	2024-11-26 05:25:50	announced

10.3390/ijms25158549;

Wesener MC, Weiler SME, Bissinger M, Klessinger TF, Rose F, Merker S, Luzarowski M, Ruppert T, Helm B, Klingm, ü, ller U, Schirmacher P, Breuhahn K, CRKL Enhances YAP Signaling through Binding and JNK/JUN Pathway Activation in Liver Cancer. Int J Mol Sci, 25(15):(2024) [pubmed]

submitter keyword: HCC

Hippo

BioID

CRK

survival

AP1

TEAD

proteomics

MS

c-Jun;

Marcin Luzarowski
contact affiliation	Core Facility for Mass Spectrometry & Proteomics Center for Molecular Biology of Heidelberg University Heidelberg, Germany
contact email	m.luzarowski@zmbh.uni-heidelberg.de
lab head
Marcin Luzarowski
contact affiliation	University of Heidelberg
contact email	m.luzarowski@zmbh.uni-heidelberg.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/2024/11/PXD058235

PRIDE project URI

• PRIDE
  1. PXD058235
     1. Label: PRIDE project
     2. Name: CRKL enhances YAP signaling through binding and JNK/JUN pathway activation in liver cancer