ArticleOncogene2014
PKA/Smurf1 signaling-mediated stabilization of Nur77 is required for anticancer drug cisplatin-induced apoptosis.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Design, synthesis, and evaluation of novel benzoylhydrazone derivatives as Nur77 modulators with potent antitumor activity against hepatocellular carcinoma.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1.Current medical science · 2023Review
- hUCMSCs reduce theca interstitial cells apoptosis and restore ovarian function in premature ovarian insufficiency rats through regulating NR4A1-mediated mitochondrial mechanisms.Reproductive biology and endocrinology : RB&E · 2022Article
- Ethyl Acetate Fraction ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
- NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.Journal of cellular and molecular medicine · 2020Article
- Posttranslational Modifications of Smurfs: Emerging Regulation in Cancer.Frontiers in oncology · 2020Review
- circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling.Molecular cancer · 2019Article
- MicroRNA-424 regulates cisplatin resistance of gastric cancer by targeting SMURF1 based on GEO database and primary validation in human gastric cancer tissues.OncoTargets and therapy · 2019Article
- Regional methylome profiling reveals dynamic epigenetic heterogeneity and convergent hypomethylation of stem cell quiescence-associated genes in breast cancer following neoadjuvant chemotherapy.Cell & bioscience · 2019Article
- The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase 2α.Scientific reports · 2018Article
- Mutually exclusive acetylation and ubiquitylation of the splicing factor SRSF5 control tumor growth.Nature communications · 2018Article
- DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA.EBioMedicine · 2017Article
- Retinoid X receptor ligand regulates RXRα/Nur77-dependent apoptosis via modulating its nuclear export and mitochondrial targeting.International journal of clinical and experimental pathology · 2017Article
- Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.Molecular neurobiology · 2016Article
- JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships.Microbiology and molecular biology reviews : MMBR · 2016Review
- Article
- Overexpression of DHX32 contributes to the growth and metastasis of colorectal cancer.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The orphan nuclear receptor Nur77 regulates diverse cellular activities, including cell proliferation, differentiation and apoptosis. The c-Jun N-terminal kinase (JNK) have a dual role in controlling the function of Nur77. While JNK-mediated phosphorylation of Nur77 positively regulates its translocation to the mitochondria to induce apoptosis, it negatively regulates the stability of Nur77. The underlying mechanism for the dual role of JNK in regulating Nur77, however, is unclear. Here, we report that E3 ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) prevents Nur77 degradation through mediating its unconventional ubiquitination, thereby mitigating the JNK-mediated downregulating effect, which leads to Nur77 accumulation and subsequent translocation to mitochondria to trigger apoptosis. In this process, protein kinase A (PKA)-mediated phosphorylation of Smurf1 at Thr306 is a prerequisite step. Accordingly, cyclic AMP/PKA signaling switches the fate of Nur77 from degradation to triggering apoptosis in chemotherapy drug cisplatin-treated cells. Hence, our study revealed a novel mechanism, by which PKA/Smurf1 antagonizes the downregulating effect of JNK on Nur77, leading to the accumulation of Nur77 for apoptosis induction triggered by cisplatin.
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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.