Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Neurodegenerative diseases are a group of chronic progressive neuronal damage disorders. The cause is unclear, most of them share a same pathological hallmark with misfold proteins accumulating in neurons. Carboxyl-terminus of Hsc70 interacting protein (CHIP) is a dual functional molecule, which has a N terminal tetratrico peptide repeat (TPR) domain that interacts with Hsc/Hsp70 complex and Hsp90 enabling CHIP to modulate the aberrant protein folding; and a C terminal U-box ubiquitin ligase domain that binds to the 26S subunit of the proteasome involved in protein degradation via ubiqutin-proteasome system. CHIP protein mediates interactions between the chaperone system and the ubiquitin-proteasome system, and plays an important role in maintaining the protein homeostasis in cells. This article reviews the molecular characteristics and physiological functions of CHIP, and its role in cellular metabolism and discusses the relationship between CHIP dysfunction and neurodegenerative diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2012.04.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CHIP protects lysosomes from CLN4 mutant-induced membrane damage.
Nat Cell Biol
August 2025
Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Understanding how cells mitigate lysosomal damage is critical for unravelling pathogenic mechanisms of lysosome-related diseases. Here we generate and characterize induced pluripotent stem cell (iPSC)-derived neurons (iNeuron) bearing ceroid lipofuscinosis neuronal 4 (CLN4)-linked DNAJC5 mutations, which revealed extensive lysosomal abnormality in mutant neurons. In vitro membrane-damaging experiments establish lysosomal damages caused by lysosome-associated CLN4 mutant aggregates, as a critical pathogenic linchpin in CLN4-associated neurodegeneration.
View Article and Find Full Text PDFElevated lactate production exacerbates PM2.5-induced pulmonary fibrosis by stabilizing TGF-β1.
J Adv Res
August 2025
Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100
Introduction: Lactate, a glycolysis byproduct, has been implicated in the fibrotic process, while transforming growth factor-beta 1 (TGF-β1) plays a central role in promoting fibrosis. Air pollution, particularly fine particulate matter (PM2.5), represents a significant environmental risk factor for the development of pulmonary fibrosis.
View Article and Find Full Text PDFStructures of Fab-stabilized CHIP reveal a conformational switch important in E3 ligase and chaperone functions.
bioRxiv
May 2025
Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA.
Carboxyl terminus of Hsc70-interacting protein (CHIP/STUB1) is a U-box E3 ligase essential for protein quality control, targeting misfolded or damaged proteins for clearance and conducting chaperone-like functions by suppressing aggregation of proteins, including tau. The previous structure of full-length CHIP identified an asymmetric homodimer in which one U-box is occluded from E2 binding, indicating an unusual half-of-sites activity. However, the flexibility of CHIP has complicated efforts to further characterize its structure and function.
View Article and Find Full Text PDFPediatric Pulmonary Hypertension is Associated With Increased Circulating Levels of BMP 7 and CHIP.
Pulm Circ
April 2025
Children's Wisconsin Milwaukee Wisconsin USA.
Pulmonary arterial endothelial and smooth muscle cell homeostasis is regulated through the bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-β) receptor pathways. Pathway imbalance results in pulmonary hypertension (PH). Each pathway has ligands and modulators influencing this balance.
View Article and Find Full Text PDFE3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.
EMBO J
February 2025
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.
View Article and Find Full Text PDF