ArticleMolecular and cellular biology2010
Tandem phosphorylation of serines 221 and 318 by protein kinase Cdelta coordinates mRNA binding and nucleocytoplasmic shuttling of HuR.
Article in Molecular and cellular biology, 2010. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
56 citing papers in PubMed, 97 citations in OpenAlex.
- Structural, biological, and biomedical implications of mRNA interactions with the master regulator HuR.NAR molecular medicine · 2025Review
- Post-transcriptional regulation by HuR in colorectal cancer: impacts on tumor progression and therapeutic strategies.Frontiers in immunology · 2025Review
- Insights into the Mode and Mechanism of Interactions Between RNA and RNA-Binding Proteins.International journal of molecular sciences · 2024Review
- Phosphorylation at the disordered N-end makes HuR accumulate and dimerize in the cytoplasm.Nucleic acids research · 2024Article
- Poly (ADP-ribose) polymerase 1 promotes HuR/ELAVL1 cytoplasmic localization and inflammatory gene expression by regulating p38 MAPK activity.Cellular and molecular life sciences : CMLS · 2024Article
- Expressions of HuR, Methyl-HuR and Phospho-HuR in Endometrial Endometrioid Adenocarcinoma Are Associated with Clinical Features.International journal of molecular sciences · 2024Article
- Targeting the RNA-Binding Protein HuR in Cancer.Cancer research · 2023Review
- Hepatitis C virus non-structural proteins modulate cellular kinases for increased cytoplasmic abundance of host factor HuR and facilitate viral replication.PLoS pathogens · 2023Article
- An AKT1-and TRIM21-mediated phosphodegron controls proteasomal degradation of HuR enabling cell survival under heat shock.iScience · 2023Article
- RNA-Binding Proteins in Bladder Cancer.Cancers · 2023Review
- HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence.Redox biology · 2022Article
- Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors.Cancers · 2022Review
- The RNA-binding protein HuR in human cancer: A friend or foe?Advanced drug delivery reviews · 2022Review
- RNA-binding proteins and their role in kidney disease.Nature reviews. Nephrology · 2022Review
- Drug delivery approaches for HuR-targeted therapy for lung cancer.Advanced drug delivery reviews · 2022Review
- Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1.Journal of cell science · 2021Article
- ELAV Proteins Bind and Stabilize C/EBP mRNA in the Induction of Long-Term Memory inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Tristetraprolin Promotes Hepatic Inflammation and Tumor Initiation but Restrains Cancer Progression to Malignancy.Cellular and molecular gastroenterology and hepatology · 2021Article
- Post-translational Control of RNA-Binding Proteins and Disease-Related Dysregulation.Frontiers in molecular biosciences · 2021Review
- 5-FU blocks shuttling of HuR mediated by PKCδ in gastric cancer cells.Translational cancer research · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stabilization of mRNA by the ubiquitous RNA binding protein human antigen R (HuR), a member of the embryonic lethal abnormal vision (ELAV) protein family, requires canonical binding to AU-rich element (ARE)-bearing target mRNA and export of nuclear HuR-mRNA complexes to the cytoplasm. In human mesangial cells (HMC) both processes are induced by angiotensin II (AngII) via protein kinase Cdelta (PKCdelta)-triggered serine phosphorylation of HuR. By testing different point-mutated Flag-tagged HuR proteins, we found that Ser 318 within RNA recognition motif 3 (RRM3) is essential for AngII-induced binding to ARE-bearing mRNA but irrelevant for nucleocytoplasmic HuR shuttling. Conversely, mutation at Ser 221 within the HuR hinge region prevents AngII-triggered HuR export without affecting mRNA binding of HuR. Using phosphorylation state-specific antibodies, we found a transient increase in HuR phosphorylation at both serines by AngII. Functionally, PKCdelta mediates the AngII-induced stabilization of prominent HuR target mRNAs, including those of cyclin A, cyclin D(1), and cyclooxygenase-2 (COX-2), and is indispensable for AngII-triggered migration and wound healing of HMC. Our data suggest a regulatory paradigm wherein a simultaneous phosphorylation at different domains by PKCdelta coordinates mRNA binding and nucleocytoplasmic shuttling of HuR, both of which events are essentially involved in the stabilization of HuR target mRNAs and relevant cell functions.
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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.