ArticleNucleic acids research2014
hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 96 citations in OpenAlex.
- The phosphoproteomic landscape of the neurological manifestations in tuberous sclerosis complex.Acta neuropathologica · 2026Article
- LncRNA ELFN1-AS1 maintains the stemness of colorectal cancer by preventing ubiquitinated degradation of the hnRNPA1 protein.Cellular and molecular life sciences : CMLS · 2026Article
- Transcriptomic and pathological analysis of the hnRNP network reveals glial involvement in frontotemporal lobar degeneration pathological subtypes.Brain communications · 2026Article
- Article
- DKC1-mediated pseudouridylation of rRNA targets hnRNP A1 to sustain IRES-dependent translation and ATF4-driven metabolic adaptation.Science advances · 2025Article
- SUMOylation and DeSUMOylation: Tug of War of Pain Signaling.Molecular neurobiology · 2025Review
- Review
- Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma.Molecular cancer · 2025Article
- S6K2 in Focus: Signaling Pathways, Post-Translational Modifications, and Computational Analysis.International journal of molecular sciences · 2024Review
- Enhanced identification of small molecules binding to hnRNPA1 via cryptic pockets mapping coupled with X-Ray fragment screening.bioRxiv : the preprint server for biology · 2024Article
- Regulation of HNRNP family by post-translational modifications in cancer.Cell death discovery · 2024Review
- Thermodynamic coupling of the tandem RRM domains of hnRNP A1 underlie its pleiotropic RNA binding functions.Science advances · 2024Article
- Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.ImmunoHorizons · 2024Article
- Ribosomal protein S6 kinase 2 (RPS6KB2) is a potential immunotherapeutic target for cancer that upregulates proinflammatory cytokines.Molecular biology reports · 2024Article
- TIMAP, a Regulatory Subunit of Protein Phosphatase 1, Inhibits In Vitro Neuronal Differentiation.International journal of molecular sciences · 2023Article
- Stress Granules as Causes and Consequences of Translation Suppression.Antioxidants & redox signaling · 2023Review
- 17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Asymmetric Dimethylation of Ribosomal S6 Kinase 2 Regulates Its Cellular Localisation and Pro-Survival Function.International journal of molecular sciences · 2023Article
- A comprehensive understanding of hnRNP A1 role in cancer: new perspectives on binding with noncoding RNA.Cancer gene therapy · 2023Review
- The RGG motif proteins: Interactions, functions, and regulations.Wiley interdisciplinary reviews. RNA · 2023Review
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
The increased cap-independent translation of anti-apoptotic proteins is involved in the development of drug resistance in lung cancer but signalling events regulating this are poorly understood. Fibroblast growth factor 2 (FGF-2) signalling-induced S6 kinase 2 (S6K2) activation is necessary, but the downstream mediator(s) coupling this kinase to the translational response is unknown. Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export. In the cytoplasm, phosphoS4/6-hnRNPA1 dissociates from these mRNAs de-repressing their IRES-mediated translation. This correlates with the phosphorylation-dependent association of hnRNPA1 with 14-3-3 leading to hnRNPA1 sumoylation on K183 and its re-import into the nucleus. A non-phosphorylatible, S4/6A mutant prevented these processes, hindering the pro-survival activity of FGF-2/S6K2 signalling. Interestingly, immunohistochemical staining of lung and breast cancer tissue samples demonstrated that increased S6K2 expression correlates with decreased cytoplasmic hnRNPA1 and increased BCL-XL expression. In short, phosphorylation on novel N-term sites of hnRNPA1 promotes translation of anti-apoptotic proteins and is indispensable for the pro-survival effects of FGF-2.
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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.