ArticleNucleic acids research2021
Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Hydrophobic Tag Degraders Overcome Endocrine-Resistant Breast Cancer by Recruiting HSP27-Mediated E3 Ligase Complex for ERα Proteasomal Degradation.Angewandte Chemie (International ed. in English) · 2026Article
- Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.Cellular & molecular biology letters · 2026Review
- Prenatal cadmium exposure and male infertility in mice: A multi-generational mechanistic study.Eco-Environment & Health · 2026Article
- Zinc Finger Protein 82 regulates p53 protein stability through histone deacetylase and enhances neo-adjuvant chemotherapy in esophageal cancer.Cell death & disease · 2025Article
- Superoxide Activates Ferroptosis via the Haber-Weiss Reaction and Enhances Age-Related Macular Degeneration.Aging cell · 2025Article
- Heat shock protein A1L restricts influenza A virus by ubiquitination of NA.Journal of virology · 2025Article
- Stub1 Acetylation by CBP/p300 Attenuates Chronic Hypoxic-Driven Pulmonary Hypertension by Suppressing HIF-2α.American journal of respiratory cell and molecular biology · 2025Article
- Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage.Cell death discovery · 2025Article
- Autophagy promotes p72 degradation and capsid disassembly during the early phase of African swine fever virus infection.Journal of virology · 2025Article
- Hyperthermia Inhibits Growth and Stemness of Esophageal Squamous Cell Carcinoma Cells Through Promoting Degradation of GLI1.Stem cells international · 2025Article
- TIP60 enhances cisplatin resistance via regulating ΔNp63α acetylation in SCC.Cell death & disease · 2024Article
- CHIP drives proteasomal degradation of NUR77 to alleviate oxidative stress and intrinsic apoptosis in cisplatin-induced nephropathy.Communications biology · 2024Article
- Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer cells.Thyroid research · 2024Article
- How MicroRNAs Command the Battle against Cancer.International journal of molecular sciences · 2024Review
- BMP Stimulation Differentially Affects Phosphorylation and Protein Stability of β-Catenin in Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Hypoxia-activated XBP1s recruits HDAC2-EZH2 to engage epigenetic suppression of ΔNp63α expression and promote breast cancer metastasis independent of HIF1α.Cell death and differentiation · 2024Article
- PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway.Oncogene · 2024Article
- Reciprocal negative feedback regulation of ATF6α and PTEN promotes prostate cancer progression.Cellular and molecular life sciences : CMLS · 2023Article
- The SWIB/MDM2 motif of UBE4B activates the p53 pathway.Molecular therapy. Nucleic acids · 2023Article
- The dual role of p63 in cancer.Frontiers in oncology · 2023Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The major clinical problem in human cancer is metastasis. Metastases are the cause of 90% of human cancer deaths. TAp63 is a critical suppressor of tumorigenesis and metastasis. ΔNp63 acts as a dominant-negative inhibitor to block the function of p53 and TAp63. Although several ubiquitin E3 ligases have been reported to regulate p63 stability, the mechanism of p63 regulation remains partially understood. Herein, we show that CHIP, an E3 ligase with a U-box domain, physically interacts with p63 and promotes p63 degradation. Notably, Hsp70 depletion by siRNA stabilizes TAp63 in H1299 cells and destabilizes ΔNp63 in SCC9 cells. Loss of Hsp70 results in a reduction in the TAp63-CHIP interaction in H1299 cells and an increase in the interaction between ΔNp63 and CHIP in SCC9 cells. Our results reveal that Hsp70 acts as a molecular switch to control CHIP-mediated ubiquitination and degradation of p63 isoforms. Furthermore, regulation of p63 by the Hsp70-CHIP axis contributes to the migration and invasion of tumor cells. Hence, our findings demonstrate that Hsp70 is a crucial regulator of CHIP-mediated ubiquitination and degradation of p63 isoforms and identify a new pathway for maintaining TAp63 or ΔNp63 stability in cancers.
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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.