ArticleThe Journal of biological chemistry2016
HBP1-mediated Regulation of p21 Protein through the Mdm2/p53 and TCF4/EZH2 Pathways and Its Impact on Cell Senescence and Tumorigenesis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 64 citations in OpenAlex.
- Targeting CDK4/6 potentiates the efficacy of anti-CD47 therapy via modulating the suppressive function of tumor-associated macrophages.Apoptosis : an international journal on programmed cell death · 2026Article
- The combined inhibitory effect of butaselen and decitabine against lung cancer cells.Scientific reports · 2026Article
- The novel thioredoxin reductase inhibitor butaselen suppresses lung cancer by inducing oxidative stress.Redox report : communications in free radical research · 2025Article
- The transcription factor HBP1 promotes ferroptosis in tumor cells by regulating the UHRF1-CDO1 axis.PLoS biology · 2023Article
- Tubular aryl hydratocarbon receptor upregulates EZH2 to promote cellular senescence in cisplatin-induced acute kidney injury.Cell death & disease · 2023Article
- HBP1 inhibits the development of type 2 diabetes mellitus through transcriptional activation of theAging · 2022Article
- Cellular senescence: the good, the bad and the unknown.Nature reviews. Nephrology · 2022Review
- Methylation of HBP1 by PRMT1 promotes tumor progression by regulating actin cytoskeleton remodeling.Oncogenesis · 2022Article
- Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma.Frontiers in oncology · 2022Review
- HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression.Journal of experimental & clinical cancer research : CR · 2021Article
- Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma.BMC cancer · 2021Article
- [Role of P21 in Resistance of Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Review
- High risk HPV detection by RNAscope in situ hybridization combined with Cdc2 protein expression by immunohistochemistry for prognosis of oropharyngeal squamous cell carcinoma.International journal of clinical and experimental pathology · 2020Article
- Article
- The HMG box transcription factor HBP1: a cell cycle inhibitor at the crossroads of cancer signaling pathways.Cellular and molecular life sciences : CMLS · 2019Review
- Anti-senescence role of heterozygous fumarate hydratase gene knockout in rat lung fibroblastsAging · 2019Article
- HOXA5 is a tumor suppressor gene that is decreased in gastric cancer.Oncology reports · 2018Article
- MiR-21 improves invasion and migration of drug-resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1.Cancer medicine · 2018Article
- HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma.Cell death & disease · 2018Article
- LncRNA-ANCR regulates the cell growth of osteosarcoma by interacting with EZH2 and affecting the expression of p21 and p27.Journal of orthopaedic surgery and research · 2017Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activity of the CDK inhibitor p21 is associated with diverse biological activities, including cell proliferation, senescence, and tumorigenesis. However, the mechanisms governing transcription of p21 need to be extensively studied. In this study, we demonstrate that the high-mobility group box-containing protein 1 (HBP1) transcription factor is a novel activator of p21 that works as part of a complex mechanism during senescence and tumorigenesis. We found that HBP1 activates the p21 gene through enhancing p53 stability by inhibiting Mdm2-mediated ubiquitination of p53, a well known positive regulator of p21. HBP1 was also found to enhance p21 transcription by inhibiting Wnt/β-catenin signaling. We identified histone methyltransferase EZH2, the catalytic subunit of polycomb repressive complex 2, as a target of Wnt/β-catenin signaling. HBP1-mediated repression of EZH2 through Wnt/β-catenin signaling decreased the level of trimethylation of histone H3 at lysine 27 of overall and specific histone on the p21 promoter, resulting in p21 transactivation. Although intricate, the reciprocal partnership of HBP1 and p21 has exceptional importance. HBP1-mediated elevation of p21 through the Mdm2/p53 and TCF4/EZH2 pathways contributes to both cellular senescence and tumor inhibition. Together, our results suggest that the HBP1 transcription factor orchestrates a complex regulation of key genes during cellular senescence and tumorigenesis with an impact on protein ubiquitination and overall histone methylation state.
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