ArticlePloS one2011
GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting Mitochondrial Therapy in the Regulation of HPV Infection and HPV-Related Cancers.Pathogens (Basel, Switzerland) · 2023Review
- GRIM19 Impedes Obesity by Regulating Inflammatory White Fat Browning and Promoting Th17/Treg Balance.Cells · 2021Article
- GRIM-19 Ameliorates Multiple Sclerosis in a Mouse Model of Experimental Autoimmune Encephalomyelitis with Reciprocal Regulation of IFNγ/Th1 and IL-17A/Th17 Cells.Immune network · 2020Article
- Benzothiazole derivative bearing amide moiety induces p53-mediated apoptosis in HPV16 positive cervical cancer cells.Investigational new drugs · 2020Article
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- Designing of CD8Biologics : targets & therapy · 2018Article
- GRIM-19: A master regulator of cytokine induced tumor suppression, metastasis and energy metabolism.Cytokine & growth factor reviews · 2017Review
- GRIM-19 Restricts HCV Replication by Attenuating Intracellular Lipid Accumulation.Frontiers in microbiology · 2017Article
- The Effect of Aging on Mitochondrial Complex I and the Extent of Oxidative Stress in the Rat Brain Cortex.Neurochemical research · 2016Article
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- Overexpression of GRIM-19, a mitochondrial respiratory chain complex I protein, suppresses hepatocellular carcinoma growth.International journal of clinical and experimental pathology · 2014Article
- Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes.Cancer cell international · 2013Article
- Tumor-derived mutations in the gene associated with retinoid interferon-induced mortality (GRIM-19) disrupt its anti-signal transducer and activator of transcription 3 (STAT3) activity and promote oncogenesis.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundOur previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this study were to determine the potential role of GRIM-19 in rescuing p53 protein and inducing cervical cancer cell apoptosis. METHODOLOGY/PRINCIPAL
findingsThe protein levels of GRIM-19 and p53 were detected in normal cervical tissues from 45 patients who underwent hysterectomy for reasons other than neoplasias of either the cervix or endometrium, and cervical cancer tissues from 60 patients with non-metastatic squamous epithelial carcinomas. Coimmunoprecipitation and GST pull-down assay were performed to examine the interaction of GRIM-19 with 18E6 and E6AP in vivo and in vitro respectively. The competition of 18E6 with E6AP in binding GRIM-19 by performing competition pull-down assays was designed to examine the disruption of E6/E6AP complex by GRIM-19. The augment of E6AP ubiquitination by GRIM-19 was detected in vivo and in vitro ubiquitination assay. The effects of GRIM-19-dependent p53 accumulation on cell proliferation, cell cycle, apoptosis were explored by MTT, flow cytometry and transmission electron microscopy respectively. The tumor suppression was detected by xenograft mouse model. CONCLUSION/SIGNIFICANCE: The levels of GRIM-19 and p53 were concurrently down regulated in cervical cancers. The restoration of GRIM-19 can induce ubiquitination and degradation of E6AP, and disrupt the E6/E6AP complex through the interaction of N-terminus of GRIM-19 with both E6 and E6AP, which protected p53 from degradation and promoted cell apoptosis. Tumor xenograft studies also revealed the suppression of p53 degradation in presence of GRIM-19. These data suggest that GRIM-19 can block E6/E6AP complex; and synergistically suppress cervical tumor growth with p53.
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