ArticleMolecular and cellular biology2005
c-Jun N-terminal kinase contributes to aberrant retinoid signaling in lung cancer cells by phosphorylating and inducing proteasomal degradation of retinoic acid receptor alpha.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 68 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- The natural L370F ERα variant confers endocrine resistance and sensitivity to ATRA in metastatic breast cancer cells.Cell communication and signaling : CCS · 2026Article
- Review
- Short-Chain Fatty Acids Calibrate RARα Activity Regulating Food Sensitization.Frontiers in immunology · 2021Article
- Differences in the early stage gene expression profiles of lung adenocarcinoma and lung squamous cell carcinoma.Oncology letters · 2019Article
- All-Trans Retinoic Acid Attenuates Fibrotic Processes by Downregulating TGF-β1/Smad3 in Early Diabetic Nephropathy.Biomolecules · 2019Article
- Retinol but not retinoic acid can enhance the glutathione level, in a manner similar to β-carotene, in a murine cultured macrophage cell line.Food science & nutrition · 2018Article
- Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma.Oncotarget · 2017Article
- JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships.Microbiology and molecular biology reviews : MMBR · 2016Review
- Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response.Molecular cell · 2015Article
- An ATRActive future for differentiation therapy in AML.Blood reviews · 2015Article
- Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.BMC cancer · 2015Article
- Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-γ via a TNF-α/JNK- mediated mechanism.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
- Vitamin A and retinoid signaling: genomic and nongenomic effects.Journal of lipid research · 2013Review
- Toxicological effects of the different substances in tobacco smoke on human embryonic development by a systems chemo-biology approach.PloS one · 2013Article
- Lipopolysaccharide induces degradation of connexin43 in rat astrocytes via the ubiquitin-proteasome proteolytic pathway.PloS one · 2013Article
- High glucose-induced repression of RAR/RXR in cardiomyocytes is mediated through oxidative stress/JNK signaling.Journal of cellular physiology · 2012Article
- Redundant roles for cJun-N-terminal kinase 1 and 2 in interleukin-1beta-mediated reduction and modification of murine hepatic nuclear retinoid X receptor alpha.Journal of hepatology · 2009Article
- Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).Nuclear receptor signaling · 2009Review
- Role of mitogen-activated protein kinase kinase 4 in cancer.Oncogene · 2007Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Retinoic acid (RA) is the ligand for nuclear RA receptors (RARs and RXRs) and is crucial for normal epithelial cell growth and differentiation. During malignant transformation, human bronchial epithelial cells acquire a block in retinoid signaling caused in part by a transcriptional defect in RARs. Here, we show that activation of c-Jun N-terminal kinase (JNK) contributes to RAR dysfunction by phosphorylating RARalpha and inducing degradation through the ubiquitin-proteasomal pathway. Analysis of RARalpha mutants and phosphopeptide mapping revealed that RARalpha residues Thr181, Ser445, and Ser461 are phosphorylated by JNK. Mutation of these residues to alanines prevented efficient ubiquitination of RARalpha and increased the stability of the protein. We investigated the importance of RARalpha phosphorylation by JNK as a mediator of retinoid resistance in lung cancer. Mice that develop lung cancer from activation of a latent K-ras oncogene had high intratumoral JNK activity and low RARalpha levels and were resistant to treatment with an RAR ligand. JNK inhibition in a human lung cancer cell line enhanced RARalpha levels, ligand-induced activity of RXR-RAR dimers, and growth inhibition by RA. These findings point to JNK as a key mediator of aberrant retinoid signaling in lung cancer cells.
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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.