ArticleCell death & disease2014
P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Physiological and molecular response of soybean to combined drought and heat stresses during flowering.BMC plant biology · 2026Article
- PA2G4 in health and disease: An underestimated multifunctional regulator.Journal of advanced research · 2025Review
- The Role of the PI3K/Akt/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments.Current atherosclerosis reports · 2025Review
- EBP1 promotes the malignant biological behaviors of kidney renal clear cell carcinoma through activation of p38/HIF-1α signaling pathway.Cancer cell international · 2024Article
- CHIP promotes CAD ubiquitination and degradation to suppress the proliferation and colony formation of glioblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis.The Journal of clinical investigation · 2024Article
- PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia.Autophagy · 2024Article
- The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.International journal of molecular sciences · 2023Review
- Targeting GRP78 suppresses oncogenic KRAS protein expression and reduces viability of cancer cells bearing various KRAS mutations.Neoplasia (New York, N.Y.) · 2022Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Cerebellar dysfunction and schizophrenia-like behavior in Ebp1-deficient mice.Molecular psychiatry · 2022Article
- EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development.BMB reports · 2021Article
- The Role of the Ubiquitin Proteasome System in Glioma: Analysis Emphasizing the Main Molecular Players and Therapeutic Strategies Identified in Glioblastoma Multiforme.Molecular neurobiology · 2021Review
- A structural view of PA2G4 isoforms with opposing functions in cancer.The Journal of biological chemistry · 2020Review
- Truncation of Pik3r1 causes severe insulin resistance uncoupled from obesity and dyslipidaemia by increased energy expenditure.Molecular metabolism · 2020Article
- The role of ubiquitination and deubiquitination in cancer metabolism.Molecular cancer · 2020Review
- Class IA PI3K regulatory subunits: p110-independent roles and structures.Biochemical Society transactions · 2020Review
- The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease.Experimental & molecular medicine · 2020Review
- Dysregulation of Epigenetic Control Contributes to Schizophrenia-Like Behavior in Ebp1International journal of molecular sciences · 2020Article
- Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The short isoform of ErbB3-binding protein 1 (Ebp1), p42, is considered to be a potent tumor suppressor in a number of human cancers, although the mechanism by which it exerts this tumor-suppressive activity is unclear. Here, we report that p42 interacts with the cSH2 domain of the p85 subunit of phosphathidyl inositol 3-kinase (PI3K), leading to inhibition of its lipid kinase activity. Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation. In this process, p42 couples p85 to the HSP70/CHIP-mediated ubiquitin-proteasomal system (UPS), thereby promoting a reduction of p85 levels both in vitro and in vivo. Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K.
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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.