DOI: 10.1091/mbc.11.5.1697. <i>HRD</i>Gene Dependence of Endoplasmic Reticulum-associated Degradation

HRDGene Dependence of Endoplasmic Reticulum-associated Degradation

10.1091/mbc.11.5.1697

Crossref journal-article

American Society for Cell Biology (ASCB)

Molecular Biology of the Cell (1076)

Abstract

Work from several laboratories has indicated that many different proteins are subject to endoplasmic reticulum (ER) degradation by a common ER-associated machinery. This machinery includes ER membrane proteins Hrd1p/Der3p and Hrd3p and the ER-associated ubiquitin-conjugating enzymes Ubc7p and Ubc6p. The wide variety of substrates for this degradation pathway has led to the reasonable hypothesis that the HRD (Hmg CoA reductase degradation) gene-encoded proteins are generally involved in ER protein degradation in eukaryotes. We have tested this model by directly comparing the HRD dependency of the ER-associated degradation for various ER membrane proteins. Our data indicated that the role of HRD genes in protein degradation, even in this highly defined subset of proteins, can vary from absolute dependence to complete independence. Thus, ER-associated degradation can occur by mechanisms that do not involve Hrd1p or Hrd3p, despite their apparently broad envelope of substrates. These data favor models in which the HRD gene-encoded proteins function as specificity factors, such as ubiquitin ligases, rather than as factors involved in common aspects of ER degradation.

Bibliography

Wilhovsky, S., Gardner, R., & Hampton, R. (2000). HRDGene Dependence of Endoplasmic Reticulum-associated Degradation. Molecular Biology of the Cell, 11(5), 1697â1708.

Authors 3

Sharon Wilhovsky (first)
Richard Gardner (additional)
Randolph Hampton (additional)

References 45 Referenced 91

10.1128/MCB.8.9.3797 / Mol. Cell. Biol. by Basson M.E. (1988)
10.1128/MMBR.59.1.63-93.1995 / Microbiol. Rev. by Boar S. (1995)
10.1091/mbc.9.1.209
10.1016/0092-8674(93)90426-Q / Cell by Chen P. (1993)
10.1128/MCB.2.8.977 / Mol. Cell. Biol. by Chevallier M.R. (1982)
10.1002/j.1460-2075.1982.tb01177.x / EMBO J. by Chevallier M.R. (1982)
10.1016/S0021-9258(18)45839-5 / J. Biol. Chem. by Chun K.T. (1990)
10.1016/S0076-6879(99)02010-8 / Methods in Enzymology by Cronin S.R. (1999)
10.1016/S0021-9258(18)32171-9 / J. Biol. Chem. by Edwards P.A. (1983)
10.1128/MCB.12.7.3288 / Mol. Cell. Biol. by Feldheim D. (1992)
10.1074/jbc.272.33.20427 / J. Biol. Chem. by Fisher E.A. (1997)
10.1096/fasebj.12.3.315 / FASEB J. by Galan J.M. (1998)
10.1091/mbc.9.9.2611
10.1093/emboj/18.21.5994 / EMBO J. by Gardner R. (1999)
10.1093/nar/24.13.2519 / Nucleic Acids Res. by Güldener U. (1996)
10.1073/pnas.94.24.12944 / Proc. Natl. Acad. Sci. USA by Hampton R.Y. (1997)
10.1091/mbc.7.12.2029
10.1073/pnas.93.2.828 / Proc. Natl. Acad. Sci. USA by Hampton R.Y. (1996)
10.1083/jcb.125.2.299 / J. Cell Biol. by Hampton R.Y. (1994)
10.1091/mbc.5.9.1039
10.1074/jbc.270.38.22329 / J. Biol. Chem. by Hill K.J. (1995)
10.1126/science.273.5282.1725 / Science by Hiller M.M. (1996)
10.1016/0378-1119(89)90358-2 / Gene by Ho S.N. (1989)
10.1146/annurev.genet.30.1.405 / Annu. Rev. Genet. by Hochstrasser M. (1996)
10.1016/0092-8674(90)90481-S / Cell by Hochstrasser M. (1990)
10.1128/JB.153.1.163-168.1983 / J. Bacteriol. by Ito H. (1983)
10.1016/0092-8674(95)90241-4 / Cell by Jensen T.J. (1995)
10.1126/science.286.5438.309 / Science by Joazeiro C.A.P. (1999)
10.1016/0092-8674(90)90104-M / Cell by Klausner R.D. (1990)
10.1002/j.1460-2075.1996.tb00411.x / EMBO J. by Knop M. (1996)
10.1016/S0092-8674(00)81881-4 / Cell by Kopito R.R. (1997)
10.1073/pnas.96.20.11364 / Proc. Natl. Acad. Sci. USA by Lorick K.L. (1999)
10.1016/S0021-9258(19)49711-1 / J. Biol. Chem. by Manolson M.F. (1992)
10.1093/emboj/17.12.3251 / EMBO J. by Mayer T.U. (1998)
10.1016/S0021-9258(18)68397-8 / J. Biol. Chem. by Nakanishi M. (1988)
10.1074/jbc.273.49.32848 / J. Biol. Chem. by Plemper R.K. (1998)
10.1242/jcs.112.22.4123 / J. Cell Sci. by Plemper R.K. (1999)
10.1101/gad.13.12.1614 / Genes Dev. by Seol J.H. (1999)
10.1128/MCB.11.2.1114 / Mol. Cell. Biol. by Silve S. (1991)
10.1126/science.284.5414.662 / Science by Skowyra D. (1999)
10.1096/fasebj.11.14.9409541 / FASEB J. by Sommer T. (1997)
10.1016/0092-8674(91)90202-A / Cell by Varshavsky A. (1991)
10.1016/0092-8674(95)90240-6 / Cell by Ward C.L. (1995)
10.1084/jem.187.6.835 / J. Exp. Med. by Yang M. (1998)
10.1074/jbc.272.33.20800 / J. Biol. Chem. by Yu H. (1997)

Dates

Type	When
Created	12 years, 1 month ago (July 2, 2013, 7:51 p.m.)
Deposited	3 years, 6 months ago (Feb. 26, 2022, 9:41 p.m.)
Indexed	1 year, 3 months ago (May 11, 2024, 4:25 a.m.)
Issued	25 years, 4 months ago (May 1, 2000)
Published	25 years, 4 months ago (May 1, 2000)
Published Print	25 years, 4 months ago (May 1, 2000)

Funders 0

None

BibTeX

@article{Wilhovsky_2000, title={HRDGene Dependence of Endoplasmic Reticulum-associated Degradation}, volume={11}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.11.5.1697}, DOI={10.1091/mbc.11.5.1697}, number={5}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Wilhovsky, Sharon and Gardner, Richard and Hampton, Randolph}, editor={Schekman, Randy W.}, year={2000}, month=may, pages={1697–1708} }

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      "first-page": "32848",
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    "date-parts": [
      [
        2000,
        5
      ]
    ]
  },
  "references-count": 45,
  "journal-issue": {
    "issue": "5",
    "published-print": {
      "date-parts": [
        [
          2000,
          5
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1091/mbc.11.5.1697"
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  "URL": "http://dx.doi.org/10.1091/mbc.11.5.1697",
  "relation": {},
  "ISSN": [
    "1059-1524",
    "1939-4586"
  ],
  "subject": [],
  "container-title-short": "MBoC",
  "published": {
    "date-parts": [
      [
        2000,
        5
      ]
    ]
  }
}