ArticleThe Journal of clinical investigation2010
Enigma negatively regulates p53 through MDM2 and promotes tumor cell survival in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- A multiomics Mendelian randomization study on PANoptosis-related genes and gastric cancer risk.The Journal of international medical research · 2026Article
- Exploring of bladder cancer immune-related genes and potential therapeutic targets based on transcriptomic data and Mendelian randomization analysis.Frontiers in immunology · 2025Article
- OGA mutant aberrantly hydrolyzes O-GlcNAc modification from PDLIM7 to modulate p53 and cytoskeleton in promoting cancer cell malignancy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MDM2: current research status and prospects of tumor treatment.Cancer cell international · 2024Review
- Regulatory and Interacting Partners of PDLIM7 in Thyroid Cancer.Current oncology (Toronto, Ont.) · 2023Article
- Review
- Role of p53 suppression in the pathogenesis of hepatocellular carcinoma.World journal of gastrointestinal pathophysiology · 2023Review
- The unexpected versatility of ALP/Enigma family proteins.Frontiers in cell and developmental biology · 2022Review
- Article
- Review
- MDM2 induces EMT via the B‑Raf signaling pathway through 14‑3‑3.Oncology reports · 2021Article
- Isoforms of the p53 Family and Gastric Cancer: A Ménage à Trois for an Unfinished Affair.Cancers · 2021Review
- Functional roles of E3 ubiquitin ligases in gastric cancer.Oncology letters · 2020Review
- DNA replication in progenitor cells and epithelial regeneration after lung injury requires the oncoprotein MDM2.JCI insight · 2019Article
- DNA methylation modifier LSH inhibits p53 ubiquitination and transactivates p53 to promote lipid metabolism.Epigenetics & chromatin · 2019Article
- Stabilization of E2-EPF UCP protein is implicated in hepatitis B virus-associated hepatocellular carcinoma progression.Cellular and molecular life sciences : CMLS · 2019Article
- Afadin cooperates with Claudin-2 to promote breast cancer metastasis.Genes & development · 2019Article
- IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner.Nucleic acids research · 2019Article
- Prognostic value of the PDLIM family in acute myeloid leukemia.American journal of translational research · 2019Article
- PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy-induced senescence.Oncogene · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human E3 ubiquitin ligase murine double minute 2 (MDM2) targets the tumor suppressor p53 for ubiquitination and degradation but also promotes its own ubiquitination and subsequent degradation. As the balance between MDM2 and p53 levels plays a crucial role in regulating cell proliferation and apoptosis, we sought to identify factors selectively inhibiting MDM2 self-ubiquitination. Here we have shown that the LIM domain protein Enigma directly interacts with MDM2 to form a ternary complex with p53 in vitro and in human hepatoma and colon carcinoma cell lines and mouse embryonic fibroblasts. We found that Enigma elicited p53 degradation by inhibiting MDM2 self-ubiquitination and increasing its ubiquitin ligase activity toward p53 in cells. Moreover, mitogenic stimuli such as serum, FGF, and HGF increased Enigma transcription via induction of serum response factor (SRF), leading to MDM2 stabilization and subsequent p53 degradation. We observed similar results in the livers of mice treated with HGF. In humans, we found SRF and Enigma coexpressed with MDM2 but not p53 in several liver and stomach tumors. Finally, we showed that Enigma promoted cell survival and chemoresistance by suppressing p53-mediated apoptosis in both cell lines and a mouse xenograft model. Our findings suggest a role for Enigma in tumorigenesis and uncover a mechanism whereby mitogens attenuate p53 antiproliferative activity through an SRF/Enigma/MDM2 pathway.
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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.