DOI: 10.1093/embo-reports/kve246. CHIP is a chaperone‐dependent E3 ligase that ubiquitylates unfolded protein

CHIP is a chaperone‐dependent E3 ligase that ubiquitylates unfolded protein

10.1093/embo-reports/kve246

Crossref journal-article

Springer Science and Business Media LLC

EMBO reports (297)

Abstract

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.

Bibliography

Murata, S., Minami, Y., Minami, M., Chiba, T., & Tanaka, K. (2001). CHIP is a chaperoneâdependent E3 ligase that ubiquitylates unfolded protein. EMBO Reports, 2(12), 1133â1138. Portico.

Authors 5

Shigeo Murata (first)
Yasufumi Minami (additional)
Michiko Minami (additional)
Tomoki Chiba (additional)
Keiji Tanaka (additional)

References 26 Referenced 481

10.1016/S0960-9822(00)00398-5
10.1128/MCB.19.6.4535
10.1126/science.292.5521.1552
10.1074/jbc.272.14.9002
10.1038/35050618
10.1146/annurev.biochem.70.1.603
10.1074/jbc.M102755200
10.1038/80384
10.1074/jbc.M002937200
{'key': 'e_1_2_5_11_1', 'article-title': 'CHIP is a U‐box‐dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation', 'author': 'Jiang J.', 'year': '2001', 'journal-title': 'J. Biol. Chem.'} / J. Biol. Chem. / CHIP is a U‐box‐dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation by Jiang J. (2001)
10.1074/jbc.274.53.37743
10.1016/S0092-8674(00)80574-7
10.1128/MCB.16.9.4773
10.1007/978-1-4615-1249-3_14
10.1038/35055162
10.1038/35050509
10.1074/jbc.271.32.19617
10.1074/jbc.275.12.9055
10.1046/j.1432-1327.2001.02145.x
10.1146/annurev.biochem.70.1.503
10.1016/S0896-6273(01)00177-5
10.1146/annurev.biochem.68.1.1015
10.1038/35056563
10.1016/S0962-8924(01)02030-X
10.1016/S0014-5793(97)01363-X
10.1083/jcb.200104079

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 6:19 p.m.)
Deposited	1 year, 8 months ago (Dec. 18, 2023, 3:55 p.m.)
Indexed	4 days, 19 hours ago (Aug. 27, 2025, 12:08 p.m.)
Issued	23 years, 9 months ago (Dec. 1, 2001)
Published	23 years, 9 months ago (Dec. 1, 2001)
Published Online	23 years, 9 months ago (Dec. 1, 2001)
Published Print	23 years, 9 months ago (Dec. 1, 2001)

Funders 0

None

BibTeX

@article{Murata_2001, title={CHIP is a chaperone‐dependent E3 ligase that ubiquitylates unfolded protein}, volume={2}, ISSN={1469-3178}, url={http://dx.doi.org/10.1093/embo-reports/kve246}, DOI={10.1093/embo-reports/kve246}, number={12}, journal={EMBO reports}, publisher={Springer Science and Business Media LLC}, author={Murata, Shigeo and Minami, Yasufumi and Minami, Michiko and Chiba, Tomoki and Tanaka, Keiji}, year={2001}, month=dec, pages={1133–1138} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        27
      ]
    ],
    "date-time": "2025-08-27T16:08:28Z",
    "timestamp": 1756310908408
  },
  "reference-count": 26,
  "publisher": "Springer Science and Business Media LLC",
  "issue": "12",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2001,
            12,
            1
          ]
        ],
        "date-time": "2001-12-01T00:00:00Z",
        "timestamp": 1007164800000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [
      "www.embopress.org"
    ],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  },
  "abstract": "<jats:p>The ubiquitin\u2013proteasome 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\u2010terminus of Hsc70\u2010interacting protein (CHIP) with a U\u2010box domain is an E3 ubiquitin\u2010ligase 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) <jats:italic>in vitro</jats:italic>, only when the unfolded substrate was captured by Hsp90 or Hsc70 and Hsp40. No ubiquitylating activity was detected in CHIP lacking the U\u2010box region. CHIP efficiently ubiquitylated denatured luciferase trapped by the C\u2010terminal region of Hsp90, which contains a CHIP binding site. CHIP also showed self\u2010ubiquitylating activity independent of target ubiquitylation. Our results indicate that CHIP can be regarded as \u2018a quality\u2010control E3\u2019 that selectively ubiquitylates unfolded protein(s) by collaborating with molecular chaperones.</jats:p>",
  "DOI": "10.1093/embo-reports/kve246",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T22:19:55Z",
    "timestamp": 1027721995000
  },
  "page": "1133-1138",
  "update-policy": "http://dx.doi.org/10.1002/crossmark_policy",
  "source": "Crossref",
  "is-referenced-by-count": 481,
  "title": "CHIP is a chaperone\u2010dependent E3 ligase that ubiquitylates unfolded protein",
  "prefix": "10.1038",
  "volume": "2",
  "author": [
    {
      "given": "Shigeo",
      "family": "Murata",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, and CREST, Japan Science and Technology Corporation (JST)  3\u201318\u201322 Honkomagome, Bunkyo\u2010ku Tokyo 113\u20108613 Japan"
        }
      ]
    },
    {
      "given": "Yasufumi",
      "family": "Minami",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Biochemistry, Oita Medical University  1\u20131 Idaigaoka, Hasama\u2010machi Oita 879\u20105593 Japan"
        }
      ]
    },
    {
      "given": "Michiko",
      "family": "Minami",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Showa Gakuin Junior College  2\u201317\u20131, Higashi\u2010Sugano, Ichikawa Chiba 272\u20100823 Japan"
        }
      ]
    },
    {
      "given": "Tomoki",
      "family": "Chiba",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, and CREST, Japan Science and Technology Corporation (JST)  3\u201318\u201322 Honkomagome, Bunkyo\u2010ku Tokyo 113\u20108613 Japan"
        }
      ]
    },
    {
      "given": "Keiji",
      "family": "Tanaka",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Oncology, Tokyo Metropolitan Institute of Medical Science, and CREST, Japan Science and Technology Corporation (JST)  3\u201318\u201322 Honkomagome, Bunkyo\u2010ku Tokyo 113\u20108613 Japan"
        }
      ]
    }
  ],
  "member": "297",
  "published-online": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_5_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(00)00398-5"
    },
    {
      "key": "e_1_2_5_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.19.6.4535"
    },
    {
      "key": "e_1_2_5_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.292.5521.1552"
    },
    {
      "key": "e_1_2_5_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.14.9002"
    },
    {
      "key": "e_1_2_5_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35050618"
    },
    {
      "key": "e_1_2_5_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.70.1.603"
    },
    {
      "key": "e_1_2_5_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M102755200"
    },
    {
      "key": "e_1_2_5_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/80384"
    },
    {
      "key": "e_1_2_5_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M002937200"
    },
    {
      "key": "e_1_2_5_11_1",
      "article-title": "CHIP is a U\u2010box\u2010dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation",
      "author": "Jiang J.",
      "year": "2001",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "e_1_2_5_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.53.37743"
    },
    {
      "key": "e_1_2_5_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80574-7"
    },
    {
      "key": "e_1_2_5_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.16.9.4773"
    },
    {
      "key": "e_1_2_5_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/978-1-4615-1249-3_14"
    },
    {
      "key": "e_1_2_5_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35055162"
    },
    {
      "key": "e_1_2_5_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35050509"
    },
    {
      "key": "e_1_2_5_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.32.19617"
    },
    {
      "key": "e_1_2_5_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.275.12.9055"
    },
    {
      "key": "e_1_2_5_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1432-1327.2001.02145.x"
    },
    {
      "key": "e_1_2_5_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.70.1.503"
    },
    {
      "key": "e_1_2_5_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(01)00177-5"
    },
    {
      "key": "e_1_2_5_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.biochem.68.1.1015"
    },
    {
      "key": "e_1_2_5_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35056563"
    },
    {
      "key": "e_1_2_5_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0962-8924(01)02030-X"
    },
    {
      "key": "e_1_2_5_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(97)01363-X"
    },
    {
      "key": "e_1_2_5_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200104079"
    }
  ],
  "container-title": "EMBO reports",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1093%2Fembo-reports%2Fkve246",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1093/embo-reports/kve246",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/full-xml/10.1093/embo-reports/kve246",
      "content-type": "application/xml",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://www.embopress.org/doi/pdf/10.1093/embo-reports/kve246",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        12,
        18
      ]
    ],
    "date-time": "2023-12-18T20:55:56Z",
    "timestamp": 1702932956000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.embopress.org/doi/10.1093/embo-reports/kve246"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  },
  "references-count": 26,
  "journal-issue": {
    "issue": "12",
    "published-print": {
      "date-parts": [
        [
          2001,
          12
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1093/embo-reports/kve246"
  ],
  "URL": "http://dx.doi.org/10.1093/embo-reports/kve246",
  "relation": {},
  "ISSN": [
    "1469-221X",
    "1469-3178"
  ],
  "subject": [],
  "container-title-short": "EMBO Reports",
  "published": {
    "date-parts": [
      [
        2001,
        12
      ]
    ]
  },
  "assertion": [
    {
      "value": "2001-08-08",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2001-10-17",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2001-12-01",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}