ArticleAging cell2015
CHIP stabilizes amyloid precursor protein via proteasomal degradation and p53-mediated trans-repression of β-secretase.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- UPS-mediated P-glycoprotein regulation in Alzheimer's disease: pharmacological implications for the amyloid pathology.Molecular biology reports · 2026Review
- STUB1-induced polyubiquitination of SIK3 in alveolar type 2 epithelial cells alleviates severity and outcomes of acute lung injury.Cell death & disease · 2026Article
- Ferroptosis-associated transcriptional factors in neurological diseases: molecular mechanisms and therapeutic prospects.Experimental & molecular medicine · 2025Review
- Ubiquitination in the Nervous System: From Molecular Mechanisms to Disease Implications.Molecular neurobiology · 2025Review
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- The autocrine motility factor receptor delays the pathological progression of Alzheimer's disease via regulating the ubiquitination-mediated degradation of APP.Alzheimer's research & therapy · 2025Article
- The ubiquitin-proteasome system in Alzheimer's disease: mechanism of action and current status of treatment.Frontiers in aging neuroscience · 2025Review
- Stub1 promotes degradation of the activated Diaph3: A negative feedback regulatory mechanism of the actin nucleator.The Journal of biological chemistry · 2024Article
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- Unraveling the genetic architecture of blood unfolded p-53 among non-demented elderlies: novel candidate genes for early Alzheimer's disease.BMC genomics · 2024Article
- Review
- ARL6IP1 mediates small-molecule-induced alleviation of Alzheimer pathology through FXR1-dependent BACE1 translation initiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer's disease-related neuropathology in cell models.The Journal of biological chemistry · 2022Article
- Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C-Terminus of Hsc70 Interacting Protein (CHIP).Chembiochem : a European journal of chemical biology · 2022Article
- Post-translational Modifications of the p53 Protein and the Impact in Alzheimer's Disease: A Review of the Literature.Frontiers in aging neuroscience · 2022Review
- The aminosterol Claramine inhibits β-secretase 1-mediated insulin receptor cleavage.The Journal of biological chemistry · 2021Article
- Age-dependent shift in the de novo proteome accompanies pathogenesis in an Alzheimer's disease mouse model.Communications biology · 2021Article
- CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.Molecules and cells · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In patient with Alzheimer's disease (AD), deposition of amyloid-beta Aβ, a proteolytic cleavage of amyloid precursor protein (APP) by β-secretase/BACE1, forms senile plaque in the brain. BACE1 activation is caused due to oxidative stresses and dysfunction of ubiquitin-proteasome system (UPS), which is linked to p53 inactivation. As partial suppression of BACE1 attenuates Aβ generation and AD-related pathology, it might be an ideal target for AD treatment. We have shown that both in neurons and in HEK-APP cells, BACE1 is a new substrate of E3-ligase CHIP and an inverse relation exists between CHIP and BACE1 level. CHIP inhibits ectopic BACE1 level by promoting its ubiquitination and proteasomal degradation, thus reducing APP processing; it stabilizes APP in neurons, thus reducing Aβ. CHIP(U) (box) domain physically interacts with BACE1; however, both U-box and TPR domain are essential for ubiquitination and degradation of BACE1. Further, BACE1 is a downstream target of p53 and overexpression of p53 decreases BACE1 level. In HEK-APP cells, CHIP is shown to negatively regulate BACE1 promoter through stabilization of p53's DNA-binding conformation and its binding upon 5' UTR element (+127 to +150). We have thus discovered that CHIP regulates p53-mediated trans-repression of BACE1 at both transcriptional and post-translational level. We propose that a CHIP-BACE1-p53 feedback loop might control APP stabilization, which could further be utilized for new therapeutic intervention in AD.
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