Home LiteratureArticle Details
PMID: 1549598 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A gene encoding a putative tyrosine phosphatase suppresses lethality of an N-end rule-dependent mutant.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 6 ·1992-03-15 ·Pages 2355-9

Ota IM, Varshavsky A

Abstract

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In the yeast Saccharomyces cerevisiae, mutational inactivation of the N-end rule pathway is neither lethal nor phenotypically conspicuous. We have used a "synthetic lethal" screen to isolate a mutant that requires the N-end rule pathway for viability. An extragenic suppressor of this mutation was cloned and found to encode a 750-residue protein with strong sequence similarities to protein phosphotyrosine phosphatases. This heat-inducible gene was named PTP2. Null ptp2 mutants grow slowly, are hypersensitive to heat, and are viable in either the presence or absence of the N-end rule pathway. We discuss possible connections between dephosphorylation of phosphotyrosine in proteins and the N-end rule pathway of protein degradation.

Related Genes
PTP2 ptp2
MeSH Terms
Amino Acid Sequence Animals Base Sequence Blotting, Northern Blotting, Southern DNA, Fungal/genetics,isolation & purification Drosophila/genetics Genes, Fungal Genes, Lethal Genotype Hot Temperature Humans Molecular Sequence Data Open Reading Frames Protein Tyrosine Phosphatases/genetics RNA, Fungal/genetics,isolation & purification Saccharomyces cerevisiae/enzymology,genetics Schizosaccharomyces/enzymology,genetics Sequence Homology, Nucleic Acid Suppression, Genetic TATA Box
Chemicals
DNA, Fungal RNA, Fungal Protein Tyrosine Phosphatases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ota I M
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Varshavsky A
References (45)
45 references, click to expand
  1. An efficient transformation procedure enabling long-term storage of competent cells of various yeast genera.
    Yeast. 1991 Oct;7(7):691-2 PMID: 1776359
  2. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance.
    Mol Gen Genet. 1984;197(2):345-6 PMID: 6394957
  3. Sindbis virus RNA polymerase is degraded by the N-end rule pathway.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8967-71 PMID: 1924357
  4. The N-end rule in bacteria.
    Science. 1991 Nov 29;254(5036):1374-7 PMID: 1962196
  5. The RET1 gene of yeast encodes the second-largest subunit of RNA polymerase III. Structural analysis of the wild-type and ret1-1 mutant alleles.
    J Biol Chem. 1991 Mar 25;266(9):5616-24 PMID: 2005101
  6. In vivo degradation of a transcriptional regulator: the yeast alpha 2 repressor.
    Cell. 1990 May 18;61(4):697-708 PMID: 2111732
  7. Universal control mechanism regulating onset of M-phase.
    Nature. 1990 Apr 5;344(6266):503-8 PMID: 2138713
  8. Cloning of a cDNA for a major human protein-tyrosine-phosphatase.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2735-9 PMID: 2157211
  9. cis-trans recognition and subunit-specific degradation of short-lived proteins.
    Nature. 1990 Jul 19;346(6281):287-91 PMID: 2165217
  10. Variation of cofactor levels in Escherichia coli. Sequence analysis and expression of the pncB gene encoding nicotinic acid phosphoribosyltransferase.
    J Biol Chem. 1990 Oct 15;265(29):17665-72 PMID: 2211655
  11. Universality and structure of the N-end rule.
    J Biol Chem. 1989 Oct 5;264(28):16700-12 PMID: 2506181
  12. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein.
    Science. 1989 Mar 24;243(4898):1576-83 PMID: 2538923
  13. A family of receptor-linked protein tyrosine phosphatases in humans and Drosophila.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8698-702 PMID: 2554325
  14. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
  15. High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules.
    Proc Natl Acad Sci U S A. 1979 Mar;76(3):1035-9 PMID: 375221
  16. Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and talin.
    Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5949-53 PMID: 1648725
  17. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes.
    Science. 1991 Jul 26;253(5018):401-6 PMID: 1650499
  18. Cyclin is degraded by the ubiquitin pathway.
    Nature. 1991 Jan 10;349(6305):132-8 PMID: 1846030
  19. Inhibition of the N-end rule pathway in living cells.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1090-4 PMID: 1899923
  20. Naming a targeting signal.
    Cell. 1991 Jan 11;64(1):13-5 PMID: 1986863
  21. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast.
    Methods Enzymol. 1991;194:281-301 PMID: 2005793
  22. Evidence for a heat shock transcription factor-independent mechanism for heat shock induction of transcription in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6550-4 PMID: 2118651
  23. Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B.
    Proc Natl Acad Sci U S A. 1990 Jul;87(13):5148-52 PMID: 2164224
  24. The recognition component of the N-end rule pathway.
    EMBO J. 1990 Oct;9(10):3179-89 PMID: 2209542
  25. The degradation signal in a short-lived protein.
    Cell. 1989 Mar 24;56(6):1019-32 PMID: 2538246
  26. Protein-tyrosine phosphatases: the other side of the coin.
    Cell. 1989 Sep 22;58(6):1013-6 PMID: 2550140
  27. Conservation of mitotic controls in fission and budding yeasts.
    Cell. 1989 Apr 21;57(2):295-303 PMID: 2649252
  28. Identifying mutations in duplicated functions in Saccharomyces cerevisiae: recessive mutations in HMG-CoA reductase genes.
    Genetics. 1987 Dec;117(4):645-55 PMID: 2828155
  29. The yeast polyubiquitin gene is essential for resistance to high temperatures, starvation, and other stresses.
    Cell. 1987 Mar 27;48(6):1035-46 PMID: 3030556
  30. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.
    Gene. 1988 Dec 30;74(2):527-34 PMID: 3073106
  31. Specificity of binding of NH2-terminal residue of proteins to ubiquitin-protein ligase. Use of amino acid derivatives to characterize specific binding sites.
    J Biol Chem. 1988 Feb 25;263(6):2693-8 PMID: 3343227
  32. The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications.
    Nucleic Acids Res. 1987 Feb 11;15(3):1281-95 PMID: 3547335
  33. Establishing homologies in protein sequences.
    Methods Enzymol. 1983;91:524-45 PMID: 6855599
  34. The short-lived MAT alpha 2 transcriptional regulator is ubiquitinated in vivo.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4606-10 PMID: 1647011
  35. Identification, cloning, and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5867-71 PMID: 1648233
  36. Cloning and expression of a yeast protein tyrosine phosphatase.
    J Biol Chem. 1991 Jul 15;266(20):12964-70 PMID: 1649172
  37. The N-end rule is mediated by the UBC2(RAD6) ubiquitin-conjugating enzyme.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7351-5 PMID: 1651502
  38. Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens.
    J Exp Med. 1987 Nov 1;166(5):1548-66 PMID: 2824653
  39. In vivo half-life of a protein is a function of its amino-terminal residue.
    Science. 1986 Oct 10;234(4773):179-86 PMID: 3018930
  40. Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation.
    Cell. 1988 Sep 9;54(6):855-64 PMID: 3044613
  41. Growth factor receptor tyrosine kinases.
    Annu Rev Biochem. 1988;57:443-78 PMID: 3052279
  42. Improved tools for biological sequence comparison.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 PMID: 3162770
  43. The molecular genetics of cancer.
    Science. 1987 Jan 16;235(4786):305-11 PMID: 3541204
  44. Isolation of genes by complementation in yeast: molecular cloning of a cell-cycle gene.
    Proc Natl Acad Sci U S A. 1980 Apr;77(4):2119-23 PMID: 6246523
  45. A fission-yeast gene encoding a protein with features of protein-tyrosine-phosphatases.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3455-9 PMID: 1849659
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.6.2355
Published
1992-03-15
Pages
2355-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48656
Subset
IM
Grants
NIDDK NIH HHS · DK39520 · United States
NIGMS NIH HHS · GM31530 · United States
Databases
GENBANK
M82872
External Links
PubMed source DOI: 10.1073/pnas.89.6.2355 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2