ArticleEndocrinology2014
The PTTG1-binding factor (PBF/PTTG1IP) regulates p53 activity in thyroid cells.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- The Role of RAC2 and PTTG1 in Cancer Biology.Cells · 2025Review
- Cell Migration in Endometriosis Responds to Omentum-Derived Molecular Cues Similar to Ovarian Cancer.International journal of molecular sciences · 2025Article
- An extracellular vesicle delivery platform based on the PTTG1IP protein.Extracellular vesicle · 2024Article
- Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer.Thyroid research · 2024Article
- Comprehensive analysis of the pituitary tumor-transforming gene (PTTG) family in lung adenocarcinoma: diagnostic, prognostic, and therapeutic implications.American journal of translational research · 2024Article
- Gene Expression Pattern ofCancers · 2023Article
- PTTG1IP (PBF) is a prognostic marker and correlates with immune infiltrate in ovarian cancer.American journal of translational research · 2023Article
- Analysis of anti-apoptotic PVT1 oncogene and apoptosis-related proteins (p53, Bcl2, PD-1, and PD-L1) expression in thyroid carcinoma.Journal of clinical laboratory analysis · 2022Article
- Establishment of an endoplasmic reticulum stress-related signature predicting outcomes of gastric adenocarcinoma patients.Frontiers in genetics · 2022Article
- Higher circular RNA_0015278 correlates with absence of extrathyroidal invasion, lower pathological tumor stages, and prolonged disease-free survival in papillary thyroid carcinoma patients.Journal of clinical laboratory analysis · 2021Article
- Hypoxia Constructing the Prognostic Model of Colorectal Adenocarcinoma and Related to the Immune Microenvironment.Frontiers in cell and developmental biology · 2021Article
- Article
- Identification of GSN and LAMC2 as Key Prognostic Genes of Bladder Cancer by Integrated Bioinformatics Analysis.Cancers · 2020Article
- Hypermethylation of theOncology letters · 2019Article
- PBF, a Proto-oncogene in Esophageal Carcinoma.Open medicine (Warsaw, Poland) · 2019Article
- PTTG and PBF Functionally Interact with p53 and Predict Overall Survival in Head and Neck Cancer.Cancer research · 2018Article
- Article
- Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer.Oncogene · 2017Article
- Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF.Endocrine-related cancer · 2017Article
- New Insights in Thyroid Cancer and p53 Family Proteins.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
The PTTG1-binding factor (PBF/PTTG1IP) has an emerging repertoire of roles, especially in thyroid biology, and functions as a protooncogene. High PBF expression is independently associated with poor prognosis and lower disease-specific survival in human thyroid cancer. However, the precise role of PBF in thyroid tumorigenesis is unclear. Here, we present extensive evidence demonstrating that PBF is a novel regulator of p53, a tumor suppressor protein with a key role in maintaining genetic stability, which is infrequently mutated in differentiated thyroid cancer. By coimmunoprecipitation and proximity-ligation assays, we show that PBF binds specifically to p53 in thyroid cells and significantly represses transactivation of responsive promoters. Further, we identify that PBF decreases p53 stability by enhancing ubiquitination, which appears dependent on the E3 ligase activity of Mdm2. Impaired p53 function was evident in a transgenic mouse model with thyroid-specific PBF overexpression (transgenic PBF mice), which had significantly increased genetic instability as indicated by fluorescent inter simple sequence repeat-PCR analysis. Consistent with this, approximately 40% of all DNA repair genes examined were repressed in transgenic PBF primary cultures, including genes with critical roles in maintaining genomic integrity such as Mgmt, Rad51, and Xrcc3. Our data also revealed that PBF induction resulted in up-regulation of the E2 enzyme Rad6 in murine thyrocytes and was associated with Rad6 expression in human thyroid tumors. Overall, this work provides novel insights into the role of the protooncogene PBF as a negative regulator of p53 function in thyroid tumorigenesis, in which PBF is generally overexpressed and p53 mutations are rare compared with other tumor types.
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