DOI: 10.1101/gad.7.2.250. The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation.

The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation.

10.1101/gad.7.2.250

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme that is required for DNA repair, damage-induced mutagenesis, and sporulation. In addition, RAD6 mediates the multiubiquitination and degradation of amino-end rule protein substrates. The structure and function of RAD6 have been remarkably conserved during eukaryotic evolution. Here, we examine the role of the extremely conserved amino terminus, which has remained almost invariant among RAD6 homologs from yeast to human. We show that RAD6 is concentrated in the nucleus and that the amino-terminal deletion mutation, rad6 delta 1-9, does not alter the location of the protein. The amino-terminal domain, however, is essential for the multiubiquitination and degradation of amino-end rule substrates. In the rad6 delta 1-9 mutant, beta-galactosidase proteins bearing destabilizing amino-terminal residues become long lived, and purified rad6 delta 1-9 protein is ineffective in ubiquitin-protein ligase (E3)-dependent protein degradation in the proteolytic system derived from rabbit reticulocytes. The amino terminus is required for physical interaction of RAD6 with the yeast UBR1-encoded E3 enzyme, as the rad6 delta 1-9 protein is defective in this respect. The rad6 delta 1-9 mutant is defective in sporulation, shows reduced efficiency of DNA repair, but is proficient in UV mutagenesis. E3-dependent protein degradation by RAD6 could be essential for sporulation and could affect the efficiency of DNA repair.

Bibliography

Watkins, J. F., Sung, P., Prakash, S., & Prakash, L. (1993). The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation. Genes & Development, 7(2), 250â261.

Authors 4

J F Watkins (first)
P Sung (additional)
S Prakash (additional)
L Prakash (additional)

References 40 Referenced 68

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10.1126/science.3018930
10.1002/j.1460-2075.1990.tb07516.x / EMBO J. / The recognition component of the N-end rule pathway. (1990)
10.1007/BF00330984
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10.1073/pnas.88.16.7351
{'key': '2021111418072032000_7.2.250.7', 'first-page': '2159', 'article-title': 'Purification of a Ras-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Purification of a Ras-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. (1988)
10.1146/annurev.cb.07.110191.000325 / Annu. Rev. Cell Biol. / Ubiquitination. (1991)
10.1126/science.2842867
10.1016/S0021-9258(18)45791-2 / J. Biol. Chem. / Ubiquitin-mediated degradation of histone H3 does not require the substrate-binding ubiquitin protein ligase E3, or attachment of polyubiquitin chains. (1990)
10.1016/S0021-9258(19)39177-X / J. Biol. Chem. / A ubiquitin-protein ligase specific for type III protein substrates. (1990)
10.1016/0968-0004(91)90101-Z
10.1128/jb.153.1.163-168.1983 / J. Bacteriol. / Transformation of intact yeast cells treated with alkali cations. (1983)
10.1038/329131a0
{'key': '2021111418072032000_7.2.250.15', 'first-page': '3807', 'article-title': 'Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs, and affects the stability of simple repetitive sequences in the genome.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs, and affects the stability of simple repetitive sequences in the genome. (1992)
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{'key': '2021111418072032000_7.2.250.20', 'first-page': '1179', 'article-title': 'Domain structure and functional analysis of the carboxy-terminal polyacidic sequence of the RAD6 protein of Saccharomyces cerevisiae.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Domain structure and functional analysis of the carboxy-terminal polyacidic sequence of the RAD6 protein of Saccharomyces cerevisiae. (1988)
10.1016/S0021-9258(18)89632-6 / J. Biol. Chem. / Functional heterogeneity of ubiquitin carrier proteins. (1985)
10.1016/S0021-9258(18)37888-8 / J. Biol. Chem. / Levels of active ubiquitin carrier proteins decline during erythroid maturation. (1988)
Prakash, S., P. Sung, and L. Prakash. 1990. Structure and function of DNA repair genes of Saccharomyces cerevisiae. In The eukaryotic nucleus: Molecular structure and macromolecular assemblies (ed. P. Strauss and S. Wilson), pp. 275–292. The Telford Press, Caldwell, NJ.
10.1016/0076-6879(91)94043-C
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Reynolds, A. and V. Lundblad. 1989. Yeast vectors and assays for expression of cloned genes. In Current protocols in molecular biology (ed. F.M. Ausubel, R. Brent, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl), vol. 2, pp. 13.6.1–13.6.4. Wiley Interscience, New York.
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10.1089/dna.1.1984.3.479

Dates

Type	When
Created	18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 9:10 p.m.)
Indexed	1 month ago (Aug. 5, 2025, 8:54 a.m.)
Issued	32 years, 7 months ago (Feb. 1, 1993)
Published	32 years, 7 months ago (Feb. 1, 1993)
Published Online	32 years, 7 months ago (Feb. 1, 1993)
Published Print	32 years, 7 months ago (Feb. 1, 1993)

Funders 0

None

BibTeX

@article{Watkins_1993, title={The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation.}, volume={7}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.7.2.250}, DOI={10.1101/gad.7.2.250}, number={2}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Watkins, J F and Sung, P and Prakash, S and Prakash, L}, year={1993}, month=feb, pages={250–261} }

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    }
  },
  "alternative-id": [
    "10.1101/gad.7.2.250"
  ],
  "URL": "http://dx.doi.org/10.1101/gad.7.2.250",
  "relation": {},
  "ISSN": [
    "0890-9369",
    "1549-5477"
  ],
  "subject": [],
  "container-title-short": "Genes Dev.",
  "published": {
    "date-parts": [
      [
        1993,
        2
      ]
    ]
  }
}