DOI: 10.1083/jcb.200111010. A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition

A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition

10.1083/jcb.200111010

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Kaposi's sarcoma-associated herpesvirus encodes two transmembrane proteins (modulator of immune recognition [MIR]1 and MIR2) that downregulate cell surface molecules (MHC-I, B7.2, and ICAM-1) involved in the immune recognition of infected cells. This downregulation results from enhanced endocytosis and subsequent endolysosomal degradation of the target proteins. Here, we show that expression of MIR1 and MIR2 leads to ubiquitination of the cytosolic tail of their target proteins and that ubiquitination is essential for their removal from the cell surface. MIR1 and MIR2 both contain cytosolic zinc fingers of the PHD subfamily, and these structures are required for this activity. In vitro, addition of a MIR2–glutathione S-transferase (GST) fusion protein to purified E1 and E2 enzymes leads to transfer of ubiquitin (Ub) to GST-containing targets in an ATP- and E2-dependent fashion; this reaction is abolished by mutation of the Zn-coordinating residues of the PHD domain. Thus, MIR2 defines a novel class of membrane-bound E3 Ub ligases that modulates the trafficking of host cell membrane proteins.

Bibliography

Coscoy, L., Sanchez, D. J., & Ganem, D. (2001). A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition. The Journal of Cell Biology, 155(7), 1265â1274.

Authors 3

Laurent Coscoy (first)
David Jesse Sanchez (additional)
Don Ganem (additional)

References 32 Referenced 240

10.1073/pnas.93.20.10990 / Proc. Natl. Acad. Sci. USA. (1996)
10.1016/S1074-7613(01)00213-8 / Immunity. (2001)
10.1093/emboj/20.1.165 / EMBO J. (2001)
10.1073/pnas.140129797 / Proc. Natl. Acad. Sci. USA. (2000)
10.1172/JCI12432 / J. Clin. Invest. (2001)
10.1242/jcs.114.11.2167 / J. Cell Sci. (2001)
10.1038/375415a0 / Nature. (1995)
10.1016/S0966-842X(98)01255-4 / Trends Microbiol. (1998)
10.1111/j.1600-065X.1999.tb01291.x / Immunol. Rev. (1999)
10.1016/S0092-8674(01)00485-8 / Cell. (2001)
10.1038/35056583 / Nat. Rev. Mol. Cell. Biol. (2001)
10.1016/S1074-7613(00)00036-4 / Immunity. (2000)
10.1128/JVI.74.11.5300-5309.2000 / J. Virol. (2000)
10.1016/S0962-8924(00)01834-1 / Trends Cell Biol. (2000)
10.1126/science.286.5438.309 / Science. (1999)
10.1073/pnas.93.21.11327 / Proc. Natl. Acad. Sci. USA. (1996)
10.1093/emboj/18.13.3616 / EMBO J. (1999)
10.1006/jmbi.2000.3766 / J. Mol. Biol. (2000)
10.1146/annurev.cellbio.16.1.591 / Annu. Rev. Cell Dev. Biol. (2000)
10.1128/jvi.71.3.1963-1974.1997 / J. Virol. (1997)
10.1006/jmbi.2000.4308 / J. Mol. Biol. (2000)
10.1146/annurev.biochem.70.1.503 / Annu. Rev. Biochem. (2001)
10.1126/science.280.5361.248 / Science. (1998)
10.1093/emboj/18.4.1081 / EMBO J. (1999)
10.1093/emboj/16.21.6325 / EMBO J. (1997)
10.1073/pnas.150240097 / Proc. Natl. Acad. Sci. USA. (2000)
10.1074/jbc.274.32.22151 / J. Biol. Chem. (1999)
10.1097/00001622-199809000-00007 / Curr. Opin. Oncol. (1998)
10.1016/S0092-8674(00)81054-5 / Cell. (1996)
10.1016/S0165-2478(97)00073-4 / Immunol. Lett. (1997)
10.1128/MCB.21.13.4110-4118.2001 / Mol. Cell. Biol. (2001)
10.1016/0092-8674(94)90215-1 / Cell. (1994)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:46 p.m.)
Deposited	2 years, 1 month ago (July 29, 2023, 4:02 a.m.)
Indexed	4 months, 2 weeks ago (April 11, 2025, 4:48 a.m.)
Issued	23 years, 8 months ago (Dec. 24, 2001)
Published	23 years, 8 months ago (Dec. 24, 2001)
Published Online	23 years, 8 months ago (Dec. 24, 2001)
Published Print	23 years, 8 months ago (Dec. 24, 2001)

Funders 0

None

BibTeX

@article{Coscoy_2001, title={A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition}, volume={155}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200111010}, DOI={10.1083/jcb.200111010}, number={7}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Coscoy, Laurent and Sanchez, David Jesse and Ganem, Don}, year={2001}, month=dec, pages={1265–1274} }

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      "DOI": "10.1242/jcs.114.11.2167",
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      "year": "2001",
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      "first-page": "415",
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      "first-page": "167",
      "DOI": "10.1111/j.1600-065X.1999.tb01291.x",
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      "year": "1999",
      "journal-title": "Immunol. Rev."
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      "first-page": "527",
      "DOI": "10.1016/S0092-8674(01)00485-8",
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      "first-page": "723",
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      "DOI": "10.1146/annurev.biochem.70.1.503",
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      "DOI": "10.1074/jbc.274.32.22151",
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      "DOI": "10.1097/00001622-199809000-00007",
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      "DOI": "10.1016/S0165-2478(97)00073-4",
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      "year": "1997",
      "journal-title": "Immunol. Lett."
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    {
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      "first-page": "4110",
      "DOI": "10.1128/MCB.21.13.4110-4118.2001",
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    {
      "key": "2023072908020904900_BIB32",
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      "first-page": "525",
      "DOI": "10.1016/0092-8674(94)90215-1",
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