ArticleStem cell reports2018
KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.
Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The trial behind it
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- The skin-specific long non-coding RNA TEDAR orchestrates late epidermal differentiation via an ERK-KLF4 cytoplasmic regulatory axis.Cell death & disease · 2026Article
- INO80 regulates promoter-associated R-loops to coordinate transcription and maintain genome stability in embryonic stem cells.Biological research · 2026Article
- Selectively Inhibition of MAPK pathway showed positive effects on Porcine embryo-derived stem cells pluripotency.Scientific reports · 2025Article
- PP2Acα Deficiency in Vascular Smooth Muscle Cells Accelerates Aortic Aneurysm and Dissection by Regulating KLF4 Phosphorylation and Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- Calmodulin-Like Protein 5 (CALML5) Expression in Squamous Cell Carcinoma of Esophagus and Oropharynx.Acta histochemica et cytochemica · 2025Article
- A Sox2 enhancer cluster regulates region-specific neural fates from mouse embryonic stem cells.G3 (Bethesda, Md.) · 2025Article
- Crosstalk between Signaling Pathways and Energy Metabolism in Pluripotency.International journal of stem cells · 2025Review
- KLF feedback loops in innate immunity.Frontiers in immunology · 2025Review
- Epsins oversee smooth muscle cell reprograming by influencing master regulators KLF4 and OCT4.bioRxiv : the preprint server for biology · 2024Article
- Trained immunity of alveolar macrophages enhances injury resolution via KLF4-MERTK-mediated efferocytosis.The Journal of experimental medicine · 2023Article
- Characterization of a Distinct State in the Continuum of Pluripotency Facilitated by Inhibition of PKCζ in Mouse Embryonic Stem Cells.Stem cell reviews and reports · 2023Article
- Maternal Undernutrition Induces Cell Signalling and Metabolic Dysfunction in Undifferentiated Mouse Embryonic Stem Cells.Stem cell reviews and reports · 2023Article
- Retention of ERK in the cytoplasm mediates the pluripotency of embryonic stem cells.Stem cell reports · 2023Article
- ATG7-mediated autophagy facilitates embryonic stem cell exit from naive pluripotency and marks commitment to differentiation.Autophagy · 2022Article
- PDGFD switches on stem cell endothelial commitment.Angiogenesis · 2022Article
- Treponema denticola Induces Interleukin-36γ Expression in Human Oral Gingival Keratinocytes via the Parallel Activation of NF-κB and Mitogen-Activated Protein Kinase Pathways.Infection and immunity · 2022Article
- Protein Tyrosine Phosphatase 1B Deficiency in Vascular Smooth Muscle Cells Promotes Perivascular Fibrosis following Arterial Injury.Thrombosis and haemostasis · 2022Article
- MiR-106b-5p Regulates the Reprogramming of Spermatogonial Stem Cells into iPSC (Induced Pluripotent Stem Cell)-Like CellsIranian biomedical journal · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation.
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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.