CHIP: a Link Between the Chaperone and Proteasome Systems

Overview

Journal Cell Stress Chaperones

Publisher Elsevier

Specialty Cell Biology

Date 2004 Apr 30

PMID 15115282

Citations 224

Authors

Holly McDonough

Cam Patterson

Affiliations

Soon will be listed here.

Abstract

CHIP, carboxy terminus of Hsc70 interacting protein, is a cytoplasmic protein whose amino acid sequence is highly conserved across species. It is most highly expressed in cardiac and skeletal muscle and brain. The primary amino acid sequence is characterized by 3 domains, a tetratricopeptide repeat (TPR) domain at its amino terminus, a U-box domain at its carboxy terminus, and an intervening charged domain. CHIP interacts with the molecular chaperones Hsc70-Hsp70 and Hsp90 through its TPR domain, whereas its U-box domain contains its E3 ubiquitin ligase activity. Its interaction with these molecular chaperones results in client substrate ubiquitylation and degradation by the proteasome. Thus, CHIP acts to tilt the folding-refolding machinery toward the degradative pathway, and it serves as a link between the two. Because protein degradation is required for healthy cellular function, CHIP's ability to degrade proteins that are the signature of disease, eg, ErbB2 in breast and ovarian cancers, could prove to be a point of therapeutic intervention.

Citing Articles

Advances in the structures, mechanisms and targeting of molecular chaperones.

Gu J, He Y, He C, Zhang Q, Huang Q, Bai S Signal Transduct Target Ther. 2025; 10(1):84.

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Recombinant antibodies inhibit enzymatic activity of the E3 ubiquitin ligase CHIP via multiple mechanisms.

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PMID: 39863102 PMC: 11883360. DOI: 10.1016/j.jbc.2025.108220.

Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP.

Nadel C, Pokhrel S, Wucherer K, Oehler A, Thwin A, Basu K Nat Commun. 2024; 15(1):7972.

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Li X, Li W, Zhang Y, Xu L, Song Y Genes Dis. 2024; 11(5):101150.

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