ArticleThe Journal of biological chemistry2010
Cytoplasmic accumulation of the RNA-binding protein HuR stabilizes the ornithine decarboxylase transcript in a murine nonmelanoma skin cancer model.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Complement Activation May Drive the Pathogenicity of Anti-α6 and Anti-β4 Integrin Antibodies In Vivo.Biomolecules · 2026Article
- The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.International journal of molecular sciences · 2024Review
- Elucidating the Role ofMedical sciences (Basel, Switzerland) · 2022Article
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- Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).Wiley interdisciplinary reviews. RNA · 2020Review
- UNR/Journal of clinical medicine · 2019Article
- Knockout of Raptor destabilizes ornithine decarboxylase mRNA and decreases binding of HuR to the ODC transcript in cells exposed to ultraviolet-B irradiation.Biochemical and biophysical research communications · 2018Article
- BAG3 regulates stability of IL-8 mRNA via interplay between HuR and miR-4312 in PDACs.Cell death & disease · 2018Article
- Myc, Oncogenic Protein Translation, and the Role of Polyamines.Medical sciences (Basel, Switzerland) · 2018Review
- The ODC 3'-Untranslated Region and 5'-Untranslated Region Contain cis-Regulatory Elements: Implications for Carcinogenesis.Medical sciences (Basel, Switzerland) · 2017Article
- ADAR2 regulates RNA stability by modifying access of decay-promoting RNA-binding proteins.Nucleic acids research · 2017Article
- Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines.Cancer growth and metastasis · 2015Review
- Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch.Biochemical and biophysical research communications · 2014Article
- Sorting out functions of sirtuins in cancer.Oncogene · 2014Review
- AngiotensinII induces HuR shuttling by post-transcriptional regulated CyclinD1 in human mesangial cells.Molecular biology reports · 2014Article
- Polyamines and cancer: implications for chemotherapy and chemoprevention.Expert reviews in molecular medicine · 2013Review
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- Ornithine decarboxylase mRNA is stabilized in an mTORC1-dependent manner in Ras-transformed cells.The Biochemical journal · 2012Article
- RNA-binding proteins as a point of convergence of the PI3K and p38 MAPK pathways.Frontiers in immunology · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. Under normal physiological conditions, polyamine content and ODC enzyme activity are highly regulated. However, the induction of ODC activity is an early step in neoplastic transformation. The studies described here use normal mouse keratinocytes (C5N cells), and spindle carcinoma cells (A5 cells) to explore the regulation of ODC in nonmelanoma skin cancer development. Previous results have shown that induction of ODC activity is both necessary and sufficient for the promotion of skin tumors. We see a marked increase in ODC enzyme activity in A5 cells compared with C5N keratinocytes, which correlates with a 4-fold stabilization of ODC mRNA. These data suggest that ODC is post-transcriptionally regulated in skin tumor development. Thus, we sought to investigate whether the ODC transcript interacts with the RNA-binding protein HuR, which is known to bind to and stabilize its target mRNAs. We show that HuR is able to bind to the ODC 3'-UTR in A5 cells but not in C5N cells. Immunofluorescence results reveal that HuR is present in both the nucleus and cytoplasm of A5 cells, whereas C5N cells exhibit strictly nuclear localization of HuR. Knockdown experiments in A5 cells showed that when HuR is depleted, ODC RNA becomes less stable, and ODC enzyme activity decreases. Together, these data support the hypothesis that HuR plays a causative role in ODC up-regulation during nonmelanoma skin cancer development by binding to and stabilizing the ODC transcript.
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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.