PXD010581 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: mass spectrometry, phosphoproteomic, TMT,Erk5 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD010581
- Label: PRIDE project
- Name: The ERK5 signalling pathway employs a KLF2-ZSCAN4 auto-regulatory module to induce embryonic 2-cell stage genes