CHIP is a chaperone‐dependent E3 ligase that ubiquitylates unfolded protein
Open accessAbstract
The ubiquitin-proteasome system catalyses the immediate destruction of misfolded or impaired proteins generated in cells, but how this proteolytic machinery recognizes abnormality of cellular proteins for selective elimination remains elusive. Here, we report that the C-terminus of Hsc70-interacting protein (CHIP) with a U-box domain is an E3 ubiquitin-ligase collaborating with molecular chaperones Hsp90 and Hsc70. Thermally denatured firefly luciferase was multiubiquitylated by CHIP in the presence of E1 and E2 (Ubc4 or UbcH5c) in vitro, only when the unfolded substrate was captured by Hsp90 or Hsc70 and Hsp40. No ubiquitylating activity was detected in CHIP lacking the U-box region. CHIP efficiently ubiquitylated denatured luciferase trapped by the C-terminal region of Hsp90, which contains a CHIP binding site. CHIP also showed self-ubiquitylating activity independent of target ubiquitylation. Our results indicate that CHIP can be regarded as 'a quality-control E3' that selectively ubiquitylates unfolded protein(s) by collaborating with molecular chaperones.
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Molecular chaperones Hsp70 and Hsp90 can recruit the co-chaperone E3 ligase CHIP, leading to ubiquitination and degradation of chaperone-bound client proteins.
“However, molecular chaperones Hsp70 and Hsp90 can also recruit the co-chaperone E3 ligase CHIP (C-terminus of Hsp70 interacting protein), which leads to ubiquitination and degradation of the chaperone-bound client proteins [56–59].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [59]
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- Authors
- Murata, S., Minami, Y., Minami, M., Chiba, T., & Tanaka, K.
- Affiliations
- Japan Science and Technology Agency (JP)
- Venue
- The EMBO Reports
- Published
- 2001-12-01
- Volume
- 2
- Issue
- 12
- Pages
- 1133-1138
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1084164
- OpenAlex
- W2097094654
- Cited by
- 574
- References
- 28
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 20 · 2023: 19 · 2022: 22 · 2021: 19 · 2020: 21 · 2019: 24 · 2018: 17 · 2017: 16 · 2016: 22 · 2015: 15 · 2014: 23 · 2013: 17 · 2012: 28
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- CHIP, Hsc70-interacting protein, E3 ubiquitin ligase, U-box domain, HSP90, Hsc70, Hsp40, molecular chaperones, protein quality control, protein denaturation, ubiquitin-proteasome system, selective protein degradation
- MeSH terms
- Animals, Coleoptera, Cattle, Hot Temperature, Heat-Shock Proteins, Humans, Ligases, Luciferases, Protein Denaturation, Blotting, Western, Protein Folding, Molecular Chaperones, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Ubiquitin, Ubiquitin-Protein Ligases, HSC70 Heat-Shock Proteins, HSP40 Heat-Shock Proteins, Mice
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