ArticleSignal transduction and targeted therapy2023
E3 ligase MG53 suppresses tumor growth by degrading cyclin D1.
Article in Signal transduction and targeted therapy, 2023. 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, 31 citations in OpenAlex.
- The combination of cyclin D1 and MRI radiomics parameters improves breast cancer diagnosis and NACT efficacy assessment.Journal of medical biochemistry · 2026Article
- Tumor-derived MG53 aggravates gastrointestinal cancer cachexia related muscle atrophy by inhibiting the TLR4/PI3K/AKT/FOXO3a signaling pathway.Frontiers in oncology · 2026Article
- Cell cycle dysregulation: a central hub in colitis-associated colorectal carcinogenesis.Frontiers in immunology · 2026Review
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- MG53 protects against septic cardiac dysfunction by ubiquitinating ATF2.Journal of advanced research · 2026Article
- Tumour Cell Size Control and Its Impact on Tumour Cell Function.Cell proliferation · 2025Review
- Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025Review
- Review
- Mitsugumin 53 drives stem cell differentiation easing intestinal injury and inflammation.Signal transduction and targeted therapy · 2025Article
- MG53 deficiency mediated skeletal muscle dysfunction in chronic obstructive pulmonary disease via impairing mitochondrial fission.Redox biology · 2025Article
- F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive cancer progression.Nature communications · 2025Article
- Pin1 as a central node in oncogenic signaling: Mechanistic insights and clinical prospects (Review).Molecular medicine reports · 2025Review
- Recombinant human mitsugumin 53: a potential therapeutic agent for multiple diseases.Frontiers in pharmacology · 2025Review
- Mycobacterial antigen Ag85B restrains Hodgkin lymphoma tumor growth by inhibiting autophagy.Oncology research · 2025Article
- Inhalation Anesthetics Play a Janus-Faced Role in Self-Renewal and Differentiation of Stem Cells.Biomolecules · 2024Review
- ARMCX1 inhibits lung adenocarcinoma progression by recruiting FBXW7 for c-Myc degradation.Biology direct · 2024Article
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.Cancer research communications · 2024Article
- Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway.Marine drugs · 2024Article
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Due to the essential role of cyclin D1 in regulating transition from G1 to S phase in cell cycle, aberrant cyclin D1 expression is a major oncogenic event in many types of cancers. In particular, the dysregulation of ubiquitination-dependent degradation of cyclin D1 contributes to not only the pathogenesis of malignancies but also the refractory to cancer treatment regiments with CDK4/6 inhibitors. Here we show that in colorectal and gastric cancer patients, MG53 is downregulated in more than 80% of tumors compared to the normal gastrointestinal tissues from the same patient, and the reduced MG53 expression is correlated with increased cyclin D1 abundance and inferior survival. Mechanistically, MG53 catalyzes the K48-linked ubiquitination and subsequent degradation of cyclin D1. Thus, increased expression of MG53 leads to cell cycle arrest at G1, and thereby markedly suppresses cancer cell proliferation in vitro as well as tumor growth in mice with xenograft tumors or AOM/DSS induced-colorectal cancer. Consistently, MG53 deficiency results in accumulation of cyclin D1 protein and accelerates cancer cell growth both in culture and in animal models. These findings define MG53 as a tumor suppressor via facilitating cyclin D1 degradation, highlighting the therapeutic potential of targeting MG53 in treating cancers with dysregulated cyclin D1 turnover.
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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.