ArticleScience signaling2013
Signaling by p38 MAPK stimulates nuclear localization of the microprocessor component p68 for processing of selected primary microRNAs.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Kinase regulation of miRNA networks in cardiometabolic disease: emerging pathways to precision therapy.Journal of molecular medicine (Berlin, Germany) · 2026Review
- DEAD-box RNA helicases with special reference to p68: Unwinding their biology, versatility, and therapeutic opportunity in cancer.Genes & diseases · 2023Review
- Altered MicroRNA Expression in Intracranial Aneurysmal Tissues: Possible Role in TGF-β Signaling Pathway.Cellular and molecular neurobiology · 2022Article
- Recent findings on the role of microRNAs in genetic kidney diseases.Molecular biology reports · 2022Review
- Regulation of MicroRNAs.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Pan-cancer analysis of the prognostic and immunological roles ofFrontiers in genetics · 2022Article
- Signaling of MK2 sustains robust AP1 activity for triple negative breast cancer tumorigenesis through direct phosphorylation of JAB1.NPJ breast cancer · 2021Article
- Article
- PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis.Nucleic acids research · 2020Article
- microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis.Frontiers in oncology · 2020Review
- RNA helicase p68 inhibits the transcription and post-transcription ofTheranostics · 2020Article
- FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus.Molecular neurobiology · 2019Article
- MicroRNA-125b-5p regulates IL-1β induced inflammatory genes via targeting TRAF6-mediated MAPKs and NF-κB signaling in human osteoarthritic chondrocytes.Scientific reports · 2019Article
- Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo.Cellular and molecular life sciences : CMLS · 2019Review
- Phosphodiesterase 7B/microRNA-200c relationship regulates triple-negative breast cancer cell growth.Oncogene · 2019Article
- Regulation of microRNA biogenesis and its crosstalk with other cellular pathways.Nature reviews. Molecular cell biology · 2019Review
- Suppression of lung cancer progression by isoliquiritigenin through its metabolite 2, 4, 2', 4'-Tetrahydroxychalcone.Journal of experimental & clinical cancer research : CR · 2018Article
- SMA1, a homolog of the splicing factor Prp28, has a multifaceted role in miRNA biogenesis in Arabidopsis.Nucleic acids research · 2018Article
- The RNA helicase DDX17 controls the transcriptional activity of REST and the expression of proneural microRNAs in neuronal differentiation.Nucleic acids research · 2018Article
- MicroRNA-101 expression is associated with JAK2V617F activity and regulates JAK2/STAT5 signaling.Leukemia · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The importance of microRNAs (miRNAs) in biological and disease processes necessitates a better understanding of the mechanisms that regulate miRNA abundance. We showed that the activities of the mitogen-activated protein kinase (MAPK) p38 and its downstream effector kinase MAPK-activated protein kinase 2 (MK2) were necessary for the efficient processing of a subset of primary miRNAs (pri-miRNAs). Through yeast two-hybrid screening, we identified p68 (also known as DDX5), a key component of the Drosha complex that processes pri-miRNAs, as an MK2-interacting protein, and we found that MK2 phosphorylated p68 at Ser(197) in cells. In wild-type mouse embryonic fibroblasts (MEFs) treated with a p38 inhibitor or in MK2-deficient (MK2(-/-)) MEFs, expression of a phosphomimetic mutant p68 fully restored pri-miRNA processing, suggesting that MK2-mediated phosphorylation of p68 was essential for this process. We found that, whereas p68 was present in the nuclei of wild-type MEFs, it was found mostly in the cytoplasm of MK2(-/-) MEFs. Nuclear localization of p68 depended on MK2-mediated phosphorylation of Ser(197). In addition, inhibition of p38 MAPK promoted the growth of wild-type MEFs and breast cancer MCF7 cells by enhancing the abundance of c-Myc through suppression of the biogenesis of the miRNA miR-145, which targets c-Myc. Because pri-miRNA processing occurs in the nucleus, our findings suggest that the p38 MAPK-MK2 signaling pathway promotes miRNA biogenesis by facilitating the nuclear localization of p68.
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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.