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2013 | 60 | 3 |

Tytuł artykułu

Homocysteine thiolactone affects protein ubiquitination in yeast

Autorzy

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
The formation of homocysteine thiolactone (HcyTl) from homocysteine occurs in all examined so far organisms including bacteria, yeast, and humans. Protein N-homocysteinylation at the ε-amino group of lysine is an adverse result of HcyTl accumulation. Since tagging of proteins by ubiquitination before their proteasomal degradation takes place at the same residue, we wondered how N-homocysteinylation may affect the ubiquitination of proteins. We used different yeast strains carrying mutations in genes involved in the homocysteine metabolism. We found positive correlation between the concentration of endogenous HcyTl and the concentration of ubiquitinated proteins. This suggests that N-homocysteinylation of proteins apparently does not preclude but rather promotes their decomposition.

Wydawca

-

Rocznik

Tom

60

Numer

3

Opis fizyczny

p.485-488,fig.,ref.

Twórcy

autor
  • Poznan University of Life Sciences, Poznan, Poland
autor
  • Poznan University of Life Sciences, Poznan, Poland

Bibliografia

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  • Glowacki R, Bald E, Jakubowski H (2010) Identification and origin of N epsilon-homocysteinyl-lysine isopeptide in humans and mice. Amino Acids 39: 1563-1569. 
  • Hershko A, Heller H, Eytan E, Kaklij G, Rose IA (1984) Role of the alpha-amino group of protein in ubiquitin-mediated protein breakdown. Proc Natl Acad Sci USA 81: 7021-7025. 
  • Jakubowski H (1990) Proofreading in vivo: editing of homocysteine by methionyl-tRNA synthetase in Escherichia coli. Proc Natl Acad Sci USA 87: 4504-4508. 
  • Jakubowski H (1991) Proofreading in vivo: editing of homocysteine by methionyl-tRNA synthetase in the yeast Saccharomyces cerevisiae. EMBO J 10: 593-598. 
  • Jakubowski H (1997) Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levels. J Biol Chem 272: 1935-1942. 
  • Jakubowski H (1999) Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels. FASEB J 13: 2277-2283. 
  • Jakubowski H (2000) Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 275: 3957-3962. 
  • Jakubowski H (2002) The determination of homocysteine-thiolactone in biological samples. Anal Biochem 308: 112-119. 
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  • Jakubowski H, Fersht AR (1981) Alternative pathways for editing non-cognate amino acids by aminoacyl-tRNA synthetases. Nucleic Acids Res 9: 3105-3117. 
  • Jakubowski H, Goldman E (1993) Synthesis of homocysteine thiolactone by methionyl-transfer RNA-synthetase in cultured-mammalian-cells. Febs Lett 317: 237-240. 
  • Jakubowski H, Perla-Kajan J, Finnell RH, Cabrera RM, Wang H, Gupta S, Kruger WD, Kraus JP, Shih DM (2009) Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in mice. Faseb J 23: 1721-1727. 
  • Jakubowski H, Perla-Kaján J, Finnell RH, Cabrera RM, Wang H, Gupta S, Kruger WD, Kraus JP, Shih DM (2009) Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in mice. FASEB J 23: 1721-1727. 
  • Jakubowski H, Zhang L, Bardeguez A, Aviv A (2000) Homocysteine thiolactone and protein homocysteinylation in human endothelial cells - Implications for atherosclerosis. Circ Res 87: 45-51. 
  • Joshua-Tor L, Xu HE, Johnston SA, Rees DC (1995) Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6. Science 269: 945-950. 
  • Kushnirov VV (2000) Rapid and reliable protein extraction from yeast. Yeast 16: 857-860. 
  • Marczak L, Sikora M, Stobiecki M, Jakubowski H (2011) Analysis of site-specific N-homocysteinylation of human serum albumin in vitro and in vivo using MALDI-ToF and LC-MS/MS mass spectrometry. J Proteomics 74: 967-974. 
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  • O'Farrell PA, Gonzalez F, Zheng W, Johnston SA, Joshua-Tor L (1999) Crystal structure of human bleomycin hydrolase, a self-compartmentalizing cysteine protease. Structure (Camb) 7: 619-627. 
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  • Perla-Kajan J, Stanger O, Luczak M, Ziolkowska A, Malendowicz LK, Twardowski T, Lhotak S, Austin RC, Jakubowski H (2008) Immunohistochemical detection of N-homocysteinylated proteins in humans and mice. Biomed Pharmacother 62: 473-479. 
  • Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM (2010) Identification, analysis, and prediction of protein ubiquitination sites. Proteins 78: 365-380. 
  • Sikora M, Jakubowski H (2009) Homocysteine editing and growth inhibition in Escherichia coli. Microbiology 155: 1858-1865. 
  • Undas A, Perla J, Lacinski M, Trzeciak W, Kazmierski R, Jakubowski H (2004) Autoantibodies against N-homocysteinylated proteins in humans - Implications for atherosclerosis. Stroke 35: 1299-1304. 
  • Wang H, Ramotar D (2002) Cellular resistance to bleomycin in Saccharomyces cerevisiae is not affected by changes in bleomycin hydrolase levels. Biochem Cell Biol 80: 789-796. 
  • Zabczyk M, Glowacki R, Machnik A, Herod P, Kazek G, Jakubowski H, Undas A (2011) Elevated concentrations of N epsilon-homocysteinyl-lysine isopeptide in acute myocardial infarction: links with ADMA formation. Clin Chem Lab Med 49: 729-735. 
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Typ dokumentu

Bibliografia

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