ArticleThe Journal of biological chemistry2013
Arsenic suppresses cell survival via Pirh2-mediated proteasomal degradation of ΔNp63 protein.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Distinct interactors define the p63 transcriptional signature in epithelial development or cancer.The Biochemical journal · 2022Article
- The RNA-binding protein HuR is a novel target of Pirh2 E3 ubiquitin ligase.Cell death & disease · 2021Article
- Pyrrolidine Dithiocarbamate Facilitates Arsenic Trioxide Against Pancreatic Cancer via Perturbing Ubiquitin-Proteasome Pathway.Cancer management and research · 2020Article
- Aberrant β-catenin expression in urothelial carcinomas in blackfoot disease-endemic areas.The Kaohsiung journal of medical sciences · 2017Article
- ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer.Cancer cell · 2016Article
- Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma.Molecular cancer · 2014Article
- RNA-binding protein RBM24 regulates p63 expression via mRNA stability.Molecular cancer research : MCR · 2014Article
- Article
- Regulation of p63 protein stability via ubiquitin-proteasome pathway.BioMed research international · 2014Review
- Pirh2: an E3 ligase with central roles in the regulation of cell cycle, DNA damage response, and differentiation.Cell cycle (Georgetown, Tex.) · 2013Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Transcription factor p63, a member of the p53 family, shares a high degree of sequence similarity with p53. Because of transcription from two distinct promoters, the p63 gene encodes two isoforms, TAp63 and ΔNp63. Although TAp63 acts as a tumor suppressor, ΔNp63 functions as an oncogene and is often overexpressed in squamous cell carcinomas. Thus, therapeutic agents targeting ΔNp63 might be used to manage tumors that overexpress ΔNp63. Here we found that arsenic trioxide, a frontline agent for acute promyelocytic leukemia, inhibits ΔNp63 but not TAp63 expression in time- and dose-dependent manners. In addition, we found that arsenic trioxide decreases the stability of ΔNp63 protein via a proteasome-dependent pathway but has little effect on the level of ΔNp63 transcript. Furthermore, we found that arsenic trioxide activates the Pirh2 promoter and consequently induces Pirh2 expression. Consistent with this, we found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, arsenic-induced degradation of ΔNp63 protein. Importantly, we found that knockdown of ΔNp63 sensitizes, whereas ectopic expression of ΔNp63 inhibits, growth suppression induced by arsenic. Together, these data suggest that arsenic degrades ΔNp63 protein at least in part via Pirh2-dependent proteolysis and that inhibition of ΔNp63 expression facilitates tumor cells to arsenic-induced death.
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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.