ArticleThe Biochemical journal2021
An ERK5-KLF2 signalling module regulates early embryonic gene expression and telomere rejuvenation in stem cells.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- A different MAPK, ERK5 plays a critical role in cell specification and differentiation.Biochemistry and biophysics reports · 2026Review
- MAPK ERK5 is a novel regulator of MHC-I in cancer cells.Cell communication and signaling : CCS · 2026Article
- ERK5 promotes autocrine expression to sustain mitogenic balance for cell fate specification in human pluripotent stem cells.Stem cell reports · 2024Article
- MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.Cell death & disease · 2023Article
- The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.Cellular and molecular life sciences : CMLS · 2022Article
- ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.Cancers · 2022Article
- Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This reveals a function for ERK5 signalling in regulating dynamically expressed early embryonic 2-cell stage (2C) genes including the mESC rejuvenation factor ZSCAN4. ERK5 signalling and ZSCAN4 induction in mESCs increases telomere length, a key rejuvenative process required for prolonged culture. Mechanistically, ERK5 promotes ZSCAN4 and 2C gene expression via transcription of the KLF2 pluripotency transcription factor. Surprisingly, ERK5 also directly phosphorylates KLF2 to drive ubiquitin-dependent degradation, encoding negative feedback regulation of 2C gene expression. In summary, our data identify a regulatory module whereby ERK5 kinase and transcriptional activities bi-directionally control KLF2 levels to pattern 2C gene transcription and a key mESC rejuvenation process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.