publication . Other literature type . Article . 2011

Mass Spectrometric Analysis of Lysine Ubiquitylation Reveals Promiscuity at Site Level

Jannie M. R. Danielsen; Kathrine B. Sylvestersen; Simon Bekker-Jensen; Damian Szklarczyk; Jon W. Poulsen; Heiko Horn; Lars J. Jensen; Niels Mailand; Michael L. Nielsen;
  • Published: 01 Mar 2011
  • Publisher: American Society for Biochemistry & Molecular Biology (ASBMB)
Abstract
The covalent attachment of ubiquitin to proteins regulates numerous processes in eukaryotic cells. Here we report the identification of 753 unique lysine ubiquitylation sites on 471 proteins using higher-energy collisional dissociation on the LTQ Orbitrap Velos. In total 5756 putative ubiquitin substrates were identified. Lysine residues targeted by the ubiquitin-ligase system show no unique sequence feature. Surface accessible lysine residues located in ordered secondary regions, surrounded by smaller and positively charged amino acids are preferred sites of ubiquitylation. Lysine ubiquitylation shows promiscuity at the site level, as evidenced by low evolution...
Subjects
Medical Subject Headings: complex mixturesbacteria
free text keywords: Research, Peptide sequence, Conserved sequence, Cell cycle, Lysine, Acetylation, SUMO protein, Molecular biology, Biochemistry, Ubiquitin, biology.protein, biology, Amino acid, chemistry.chemical_classification, chemistry
75 references, page 1 of 5

1.Yang X. J. (2005) Multisite protein modification and intramolecular signaling. Oncogene 24, 1653–1662 15744326 [PubMed]

2.Mann M.Jensen O. N. (2003) Proteomic analysis of post-translational modifications. Nat. Biotechnol. 21, 255–261 12610572 [PubMed]

3.Ciechanover A. (1994) The ubiquitin-proteasome proteolytic pathway. Cell 79, 13–21 7923371 [OpenAIRE] [PubMed]

4.Scheffner M.Nuber U.Huibregtse J. M. (1995) Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 373, 81–83 7800044 [OpenAIRE] [PubMed]

5.Hussain S.Zhang Y.Galardy P. J. (2009) DUBs and cancer: the role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors. Cell Cycle 8, 1688–1697 19448430 [PubMed]

6.Love K. R.Catic A.Schlieker C.Ploegh H. L. (2007) Mechanisms, biology and inhibitors of deubiquitinating enzymes. Nat. Chem. Biol. 3, 697–705 17948018 [OpenAIRE] [PubMed]

7.Reyes-Turcu F. E.Ventii K. H.Wilkinson K. D. (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Ann. Rev. Biochem. 78, 363–397 19489724 [OpenAIRE] [PubMed]

8.Petroski M. D. (2008) The ubiquitin system, disease, and drug discovery. BMC Biochem. 9 Suppl 1, S7 19007437 [OpenAIRE] [PubMed]

9.Paul S. (2008) Dysfunction of the ubiquitin-proteasome system in multiple diseas e conditions: therapeutic approaches. Bioessays 30, 1172–1184 18937370 [OpenAIRE] [PubMed]

10.Singhal S.Taylor M. C.Baker R. T. (2008) Deubiquitylating enzymes and disease. BMC Biochem. 9 Suppl 1, S3 19007433 [OpenAIRE] [PubMed]

11.Olsen J. V.Blagoev B.Gnad F.Macek B.Kumar C.Mortensen P.Mann M. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635–648 17081983 [OpenAIRE] [PubMed]

12.Dephoure N.Zhou C.Villén J.Beausoleil S. A.Bakalarski C. E.Elledge S. J.Gygi S. P. (2008) A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 105, 10762–10767 18669648 [OpenAIRE] [PubMed]

13.Choudhary C.Kumar C.Gnad F.Nielsen M. L.Rehman M.Walther T. C.Olsen J. V.Mann M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834–840 19608861 [OpenAIRE] [PubMed]

14.Zielinska D. F.Gnad F.Wiśniewski J. R.Mann M. (2010) Precision mapping of an in vivo N-glycoproteome reveals rigid topological and sequence constraints. Cell 141, 897–907 20510933 [OpenAIRE] [PubMed]

15.Peng J.Schwartz D.Elias J. E.Thoreen C. C.Cheng D.Marsischky G.Roelofs J.Finley D.Gygi S. P. (2003) A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol. 21, 921–926 12872131 [PubMed]

75 references, page 1 of 5
Abstract
The covalent attachment of ubiquitin to proteins regulates numerous processes in eukaryotic cells. Here we report the identification of 753 unique lysine ubiquitylation sites on 471 proteins using higher-energy collisional dissociation on the LTQ Orbitrap Velos. In total 5756 putative ubiquitin substrates were identified. Lysine residues targeted by the ubiquitin-ligase system show no unique sequence feature. Surface accessible lysine residues located in ordered secondary regions, surrounded by smaller and positively charged amino acids are preferred sites of ubiquitylation. Lysine ubiquitylation shows promiscuity at the site level, as evidenced by low evolution...
Subjects
Medical Subject Headings: complex mixturesbacteria
free text keywords: Research, Peptide sequence, Conserved sequence, Cell cycle, Lysine, Acetylation, SUMO protein, Molecular biology, Biochemistry, Ubiquitin, biology.protein, biology, Amino acid, chemistry.chemical_classification, chemistry
75 references, page 1 of 5

1.Yang X. J. (2005) Multisite protein modification and intramolecular signaling. Oncogene 24, 1653–1662 15744326 [PubMed]

2.Mann M.Jensen O. N. (2003) Proteomic analysis of post-translational modifications. Nat. Biotechnol. 21, 255–261 12610572 [PubMed]

3.Ciechanover A. (1994) The ubiquitin-proteasome proteolytic pathway. Cell 79, 13–21 7923371 [OpenAIRE] [PubMed]

4.Scheffner M.Nuber U.Huibregtse J. M. (1995) Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 373, 81–83 7800044 [OpenAIRE] [PubMed]

5.Hussain S.Zhang Y.Galardy P. J. (2009) DUBs and cancer: the role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors. Cell Cycle 8, 1688–1697 19448430 [PubMed]

6.Love K. R.Catic A.Schlieker C.Ploegh H. L. (2007) Mechanisms, biology and inhibitors of deubiquitinating enzymes. Nat. Chem. Biol. 3, 697–705 17948018 [OpenAIRE] [PubMed]

7.Reyes-Turcu F. E.Ventii K. H.Wilkinson K. D. (2009) Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Ann. Rev. Biochem. 78, 363–397 19489724 [OpenAIRE] [PubMed]

8.Petroski M. D. (2008) The ubiquitin system, disease, and drug discovery. BMC Biochem. 9 Suppl 1, S7 19007437 [OpenAIRE] [PubMed]

9.Paul S. (2008) Dysfunction of the ubiquitin-proteasome system in multiple diseas e conditions: therapeutic approaches. Bioessays 30, 1172–1184 18937370 [OpenAIRE] [PubMed]

10.Singhal S.Taylor M. C.Baker R. T. (2008) Deubiquitylating enzymes and disease. BMC Biochem. 9 Suppl 1, S3 19007433 [OpenAIRE] [PubMed]

11.Olsen J. V.Blagoev B.Gnad F.Macek B.Kumar C.Mortensen P.Mann M. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635–648 17081983 [OpenAIRE] [PubMed]

12.Dephoure N.Zhou C.Villén J.Beausoleil S. A.Bakalarski C. E.Elledge S. J.Gygi S. P. (2008) A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 105, 10762–10767 18669648 [OpenAIRE] [PubMed]

13.Choudhary C.Kumar C.Gnad F.Nielsen M. L.Rehman M.Walther T. C.Olsen J. V.Mann M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834–840 19608861 [OpenAIRE] [PubMed]

14.Zielinska D. F.Gnad F.Wiśniewski J. R.Mann M. (2010) Precision mapping of an in vivo N-glycoproteome reveals rigid topological and sequence constraints. Cell 141, 897–907 20510933 [OpenAIRE] [PubMed]

15.Peng J.Schwartz D.Elias J. E.Thoreen C. C.Cheng D.Marsischky G.Roelofs J.Finley D.Gygi S. P. (2003) A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol. 21, 921–926 12872131 [PubMed]

75 references, page 1 of 5
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