ArticleOncotarget2017
BTK blocks the inhibitory effects of MDM2 on p53 activity.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Glycosylation in cancer: mechanisms, diagnostic markers, and therapeutic applications.Molecular and cellular biochemistry · 2025Review
- Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome- paving the path towards precision medicine: a case report.Journal of cancer research and clinical oncology · 2025Article
- Bruton's Tyrosine Kinase Inhibitors: A Versatile Therapeutic Approach for Cancer, Autoimmune Disorders, GVHD and COVID-19.Mini reviews in medicinal chemistry · 2025Review
- Article
- Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival.Life science alliance · 2021Article
- Runt related transcription factor-1 plays a central role in vessel co-option of colorectal cancer liver metastases.Communications biology · 2021Article
- The RNA-binding protein HuR is a novel target of Pirh2 E3 ubiquitin ligase.Cell death & disease · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer.Cell death discovery · 2020Review
- Amelioration of age-related brain function decline by Bruton's tyrosine kinase inhibition.Aging cell · 2020Article
- BTK Has Potential to Be a Prognostic Factor for Lung Adenocarcinoma and an Indicator for Tumor Microenvironment Remodeling: A Study Based on TCGA Data Mining.Frontiers in oncology · 2020Article
- Resveratrol induces p53 in colorectal cancer through SET7/9.Oncology letters · 2019Article
- Protoporphyrin IX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and induces apoptosis in B-cell chronic lymphocytic leukemia cells.Cell death discovery · 2019Article
- BTK: a two-faced effector in cancer and tumour suppression.Cell death & disease · 2018Article
- Erythropoietin Intensifies the Proapoptotic Activity of LFM-A13 in Cells and in a Mouse Model of Colorectal Cancer.International journal of molecular sciences · 2018Article
- BTK modulates p73 activity to induce apoptosis independently of p53.Cell death discovery · 2018Article
- Systematic Analysis of Spleen Tyrosine Kinase Expression and its Clinical Outcomes in Various Cancers.Saudi journal of medicine & medical sciencesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p53 is a tumour suppressor that is activated in response to various types of stress. It is regulated by a complex pattern of over 50 different post-translational modifications, including ubiquitination by the E3 ligase MDM2, which leads to its proteasomal degradation. We have previously reported that expression of Bruton's Tyrosine Kinase (BTK) induces phosphorylation of p53 at the N-terminus, including Serine 15, and increases its protein levels and activity. The mechanisms involved in this process are not completely understood. Here, we show that BTK also increases MDM2 and is necessary for MDM2 upregulation after DNA damage, consistent with what we have shown for other p53 target genes. Moreover, we found that BTK binds to MDM2 on its PH domain and induces its phosphorylation. This suggested a negative regulation of MDM2 functions by BTK, supported by the fact BTK expression rescued the inhibitory effects of MDM2 on p53 transcriptional activity. Indeed, we observed that BTK mediated the loss of the ubiquitination activity of MDM2, a process that was dependent on the phosphorylation functions of BTK. Our data together shows that the kinase activity of BTK plays an important role in disrupting the MDM2-p53 negative feedback loop by acting at different levels, including binding to and inactivation of MDM2. This study provides a potential mechanism to explain how BTK modulates p53 functions.
Indexed as
Identifiers
What OpenQuestion holds
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.