PXD010581

PXD010581 is an original dataset announced via ProteomeXchange.

Title	The ERK5 signalling pathway employs a KLF2-ZSCAN4 auto-regulatory module to induce embryonic 2-cell stage genes
Description	The ERK5 MAP kinase signalling pathway was recently discovered as a driver of naïve pluripotency in mouse Embryonic Stem Cells (mESCs). However, the molecular functions of ERK5 in mESCs have not been investigated. Here, we employ combinatorial mESC proteomics to identify ERK5 target genes and substrates. Global proteomic profiling reveals ZSCAN4 and other 2-cell stage genes as transcriptional targets of the ERK5 pathway. ZSCAN4 expression is specifically induced by ERK5-dependent transcription of the core pluripotency factor KLF2. Additionally, ERK5 directly phosphorylates tandem KLF2 Thr-Pro/Ser-Pro motifs identified by phosphoproteomics to recruit the FBXW7-CUL1 E3 ligase, promoting KLF2 ubiquitylation and degradation. ERK5 phosphorylation of KLF2 thereby provides negative-feedback control to restrain transcriptional induction of ZSCAN4. Our data uncover an auto-regulatory module by which ERK5 co-opts KLF2 to pattern ZSCAN4 expression. This study provides the first molecular insight into ERK5 functions in mESCs, and suggests a novel role for ERK5 signalling in stem cell rejuvenation
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:30:29.354.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Trost
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	deaminated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-26 09:10:35	ID requested
1	2021-11-29 06:53:14	announced
⏵ 2	2024-10-22 05:30:29	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: mass spectrometry, phosphoproteomic, TMT,Erk5

Matthias Trost
contact affiliation	Prof Matthias Trost Chair of Proteomics Newcastle University Faculty of Medical Sciences Institute for Cell and Molecular Biosciences Framlington Place Newcastle-upon-Tyne NE2 4HH, UK
contact email	matthias.trost@ncl.ac.uk
lab head
Matthias Trost
contact affiliation	Newcastle University
contact email	matthias.trost@ncl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010581
     1. Label: PRIDE project
     2. Name: The ERK5 signalling pathway employs a KLF2-ZSCAN4 auto-regulatory module to induce embryonic 2-cell stage genes