ArticleJournal of the National Cancer Institute2012
Acceleration of gastric tumorigenesis through MKRN1-mediated posttranslational regulation of p14ARF.
Article in Journal of the National Cancer Institute, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- MKRN1 suppresses cuproptosis in colorectal cancer through ubiquitin-dependent regulation of SLC31A1.Biological procedures online · 2026Article
- Linalool targets NR3C2 to inhibit NF-κB-mediated gastric cancer progression.Cell division · 2026Article
- MKRN1 degrades AGC1 to trigger chemotherapy resistance of colorectal Cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- SUMOylation of the lysine-less tumor suppressor p14ARF counters ubiquitylation-dependent degradation.Cell death & disease · 2025Article
- SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.Science advances · 2024Article
- MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.Journal of experimental & clinical cancer research : CR · 2023Article
- UPS: Opportunities and challenges for gastric cancer treatment.Frontiers in oncology · 2023Review
- Helicobacter pylori pathogen inhibits cellular responses to oncogenic stress and apoptosis.PLoS pathogens · 2022Article
- CRL2Oncogene · 2022Article
- An Update to Hallmarks of Cancer.Cureus · 2022Review
- Identification of Biomarkers Associated With CD8+ T Cells in Coronary Artery Disease and Their Pan-Cancer Analysis.Frontiers in immunology · 2022Article
- PRMT1 promotes the tumor suppressor function of p14The EMBO journal · 2021Article
- Roles of E3 ubiquitin ligases in gastric cancer carcinogenesis and their effects on cisplatin resistance.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Review
- Jab1 promotes gastric cancer tumorigenesis via non-ubiquitin proteasomal degradation of p14ARF.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- Functional roles of E3 ubiquitin ligases in gastric cancer.Oncology letters · 2020Review
- Post-Translational Regulation of ARF: Perspective in Cancer.Biomolecules · 2020Review
- Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway.International journal of molecular sciences · 2019Review
- Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase.Metabolism: clinical and experimental · 2019Article
- Helicobacter pylori pathogen regulates p14ARF tumor suppressor and autophagy in gastric epithelial cells.Oncogene · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe investigated whether Makorin ring finger protein 1 (MKRN1), an E3 ligase, affects p14ARF-associated cellular senescence and tumorigenesis by posttranslational modification in gastric tumorigenesis.
methodsA link between MKRN1 and ARF was examined in MKRN1 null mouse embryonic fibroblasts (MEFs) and in human fibroblasts and gastric cancer cells by silencing MKRN1 using small interfering RNA (siRNA) and short hairpin RNA (shRNA). Ubiquitination and proteasomal degradation assays were used to assess p14ARF degradation associated with MKRN1. MKRN1 and p14ARF expression levels were analyzed with immunohistochemistry in malignant and normal tissues from gastric cancer patients and with χ(2) tests. The tumor growth of gastric cancer cells stably expressing MKRN1 shRNA, p14ARF shRNA, or both was examined in mouse xenograft models (n = 4-6) and analyzed with unpaired t tests. All statistical tests were two-sided.
resultsMKRN1 knockout MEFs exhibited premature senescence and growth retardation with increased p19ARF protein expression. Similar results were obtained for human fibroblasts or gastric cancer cell lines by MKRN1 knockdown. Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation. A statistically significant association was shown between MKRN1 overexpression and p14ARF underexpression (P = .016). Xenograft analyses using p53-functional AGS or -dysfunctional SNU601 cells displayed statistically significant tumor growth retardation by silencing MKRN1, which was reversed under depletion of p14ARF (AGS cells, MKRN1 knockdown tumors vs MKRN1 and p14ARF knockdown tumors: 164.6 vs 464.8mm(3), difference = 300.2mm(3), 95% CI = 189.1 to 411.3mm(3), P < .001).
conclusionsWe demonstrated that MKRN1 functions as a novel E3 ligase of p14ARF and that it potentially regulates cellular senescence and tumorigenesis in gastric cancer.
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