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Bogdan Polevoda

TitleResearch Assistant Professor
InstitutionSchool of Medicine and Dentistry
DepartmentBiochemistry and Biophysics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester NY 14642
 
 Overview
Although there are only 20 primary amino acids that are encoded during translation, it is found that more than 100 different enzymatically modified amino acid residues are known from different proteins. The two cotranslational processes, cleavage of N-terminal methionine and N-terminal acetylation (N- acetylation), are by far the most common modifications, occurring on the vast majority of eukaryotic proteins.

N-acetylation is an enzyme-catalyzed reaction in which the protein N-terminal residues, such as a-Ser, a-Ala, a-Met, etc., accepts the acetyl group from acetyl-CoA. This modification neutralizes positive charges that may influence the protein function, stability, interaction with other molecules, or other subsequent modifications. The reaction is catalyzed by a number of acetyltransferases (NATs) that have been found in all kingdoms, prokaryotes, archaea and eukaryotes. N-acetylation is occurring on approximately 80-90% of the different varieties of cytosolic mammalian proteins, on about 50% of yeast proteins, but rarely on prokaryotic or archaeal proteins. It is believed that N-acetylation is cotranslational only in eukaryotes but not in prokaryotes, where it is posttranslational. In vitro studies indicated that NATs act on the newly synthesized polypeptide when there are between 25 to 50 residues extruding from the ribosome.

In our studies with yeast Saccharomyces cerevisiae we revealed that N-terminal protein acetylation occurs mainly by action of three NATs, NatA, NatB and NatC, which contain Ard1p, Nat3p and Mak3p catalytic subunits, respectively, and which act on groups of substrates, each containing degenerate motifs. NatA acetylates a subclasses of proteins with Ser-, Ala-, Gly- and Thr- termini; NatB acetylates Met-Glu- and Met-Asp- termini; and NatC acetylates a rare class of Met- termini. Recently, an additional NAT, Nat4p (NatD) was shown to acetylate the N-termini of histones H2A and H4, Ser-Gly-Gly-Lys-Gly- and Ser-Gly-Arg-Gly-Arg-, respectively. However, only subsets of proteins with any of these N-terminal residues are acetylated, and none of these residues guarantee acetylation, indicating that the enzymes recognize some structural characteristics of the N-terminal portion in addition to a particular amino acid sequence. Overall, the patterns of N-terminally acetylated proteins and orthologous genes possibly encoding NATs suggest that yeast and higher eukaryotes have the same or very similar system for N-terminal acetylation.

Three major NATs, NatA, NatB and NatC are heteromeric protein complexes containing at least one auxiliary subunit in addition to catalytic subunit, in contrast to NatD that appears to have no additional subunit. Interestingly, NatA contains two potential catalytic subunits, Ard1p and hypothetical acetyltransferase Nat5p, presumably with different substrate specificities. It has been shown recently that Nat1p is attached to the ribosome. In our experiments we demonstrated that Ard1p, Mak3p and Nat4p are cytoplasmic proteins, which were co-localized with polyribosomes in sucrose gradient. We suggested that the three auxiliary subunits, Nat1p, Mdm20p and Mak10p, may play a role in NAT attachment to the ribosome and recognition of a proper protein substrate.

 
 Selected Publications
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  1. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31; 109(31):12449-54.
    View in: PubMed
  2. Kamita M, Kimura Y, Ino Y, Kamp RM, Polevoda B, Sherman F, Hirano H. N(a)-Acetylation of yeast ribosomal proteins and its effect on protein synthesis. J Proteomics. 2011 Apr 1; 74(4):431-41.
    View in: PubMed
  3. Polevoda B, Arnesen T, Sherman F. A synopsis of eukaryotic Nalpha-terminal acetyltransferases: nomenclature, subunits and substrates. BMC Proc. 2009; 3 Suppl 6:S2.
    View in: PubMed
  4. Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, Varhaug JE, Vandekerckhove J, Lillehaug JR, Sherman F, Gevaert K. Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc Natl Acad Sci U S A. 2009 May 19; 106(20):8157-62.
    View in: PubMed
  5. Polevoda B, Hoskins J, Sherman F. Properties of Nat4, an N(alpha)-acetyltransferase of Saccharomyces cerevisiae that modifies N termini of histones H2A and H4. Mol Cell Biol. 2009 Jun; 29(11):2913-24.
    View in: PubMed
  6. Polevoda B, Brown S, Cardillo TS, Rigby S, Sherman F. Yeast N(alpha)-terminal acetyltransferases are associated with ribosomes. J Cell Biochem. 2008 Feb 1; 103(2):492-508.
    View in: PubMed
  7. Polevoda B, Sherman F. Methylation of proteins involved in translation. Mol Microbiol. 2007 Aug; 65(3):590-606.
    View in: PubMed
  8. Polevoda B, Panciera Y, Brown SP, Wei J, Sherman F. Phenotypes of yeast mutants lacking the mitochondrial protein Pet20p. Yeast. 2006 Jan 30; 23(2):127-39.
    View in: PubMed
  9. Polevoda B, Span L, Sherman F. The yeast translation release factors Mrf1p and Sup45p (eRF1) are methylated, respectively, by the methyltransferases Mtq1p and Mtq2p. J Biol Chem. 2006 Feb 3; 281(5):2562-71.
    View in: PubMed
  10. Polevoda B, Sherman F. Composition and function of the eukaryotic N-terminal acetyltransferase subunits. Biochem Biophys Res Commun. 2003 Aug 15; 308(1):1-11.
    View in: PubMed
  11. Polevoda B, Cardillo TS, Doyle TC, Bedi GS, Sherman F. Nat3p and Mdm20p are required for function of yeast NatB Nalpha-terminal acetyltransferase and of actin and tropomyosin. J Biol Chem. 2003 Aug 15; 278(33):30686-97.
    View in: PubMed
  12. Polevoda B, Sherman F. N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins. J Mol Biol. 2003 Jan 24; 325(4):595-622.
    View in: PubMed
  13. Kimura Y, Saeki Y, Yokosawa H, Polevoda B, Sherman F, Hirano H. N-Terminal modifications of the 19S regulatory particle subunits of the yeast proteasome. Arch Biochem Biophys. 2003 Jan 15; 409(2):341-8.
    View in: PubMed
  14. Polevoda B, Sherman F. The diversity of acetylated proteins. Genome Biol. 2002; 3(5):reviews0006.
    View in: PubMed
  15. Polevoda B, Sherman F. NatC Nalpha-terminal acetyltransferase of yeast contains three subunits, Mak3p, Mak10p, and Mak31p. J Biol Chem. 2001 Jun 8; 276(23):20154-9.
    View in: PubMed
  16. Polevoda B, Sherman F. Nalpha -terminal acetylation of eukaryotic proteins. J Biol Chem. 2000 Nov 24; 275(47):36479-82.
    View in: PubMed
  17. Roublevskaia IN, Polevoda BV, Ludlow JW, Haake AR. Induced G2/M arrest and apoptosis in human epidermoid carcinoma cell lines by semisynthetic drug Ukrain. Anticancer Res. 2000 Sep-Oct; 20(5A):3163-7.
    View in: PubMed
  18. Polevoda B, Martzen MR, Das B, Phizicky EM, Sherman F. Cytochrome c methyltransferase, Ctm1p, of yeast. J Biol Chem. 2000 Jul 7; 275(27):20508-13.
    View in: PubMed
  19. Kimura Y, Takaoka M, Tanaka S, Sassa H, Tanaka K, Polevoda B, Sherman F, Hirano H. N(alpha)-acetylation and proteolytic activity of the yeast 20 S proteasome. J Biol Chem. 2000 Feb 18; 275(7):4635-9.
    View in: PubMed
  20. Roublevskaia IN, Haake AR, Ludlow JW, Polevoda BV. Induced apoptosis in human prostate cancer cell line LNCaP by Ukrain. Drugs Exp Clin Res. 2000; 26(5-6):141-7.
    View in: PubMed
  21. Roublevskaia IN, Haake AR, Polevoda BV. Bcl-2 overexpression protects human keratinocyte cells from Ukrain-induced apoptosis but not from G2/M arrest. Drugs Exp Clin Res. 2000; 26(5-6):149-56.
    View in: PubMed
  22. Arnold RJ, Polevoda B, Reilly JP, Sherman F. The action of N-terminal acetyltransferases on yeast ribosomal proteins. J Biol Chem. 1999 Dec 24; 274(52):37035-40.
    View in: PubMed
  23. Polevoda B, Norbeck J, Takakura H, Blomberg A, Sherman F. Identification and specificities of N-terminal acetyltransferases from Saccharomyces cerevisiae. EMBO J. 1999 Nov 1; 18(21):6155-68.
    View in: PubMed
  24. Maines MD, Polevoda B, Coban T, Johnson K, Stoliar S, Huang TJ, Panahian N, Cory-Slechta DA, McCoubrey WK. Neuronal overexpression of heme oxygenase-1 correlates with an attenuated exploratory behavior and causes an increase in neuronal NADPH diaphorase staining. J Neurochem. 1998 May; 70(5):2057-69.
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  25. Maines MD, Polevoda BV, Huang TJ, McCoubrey WK. Human biliverdin IXalpha reductase is a zinc-metalloprotein. Characterization of purified and Escherichia coli expressed enzymes. Eur J Biochem. 1996 Jan 15; 235(1-2):372-81.
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  26. Perepnikhatka VI, Polevoda BV. [The genetic aspects of the study of Pseudomonas syringae bacteria]. Mikrobiol Z. 1995 May-Jun; 57(3):84-97.
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  27. Zaverukha VB, Polevoda BV, Polishchuk LV, Matseliukh BP. [The cloning of fragments of the streptomycete plasmid pSG1912 as a part of the vector pUC19]. Mikrobiol Zh. 1992 Sep-Oct; 54(5):30-5.
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  28. Polishchuk LV, Polevoda BV, Zaverukha VB, Matseliukh BP. [The stability of plasmid pSG 1912 inheritance by the cells of Streptomyces globisporus 1912 and of heterologous streptomycete strains]. Mikrobiol Zh. 1992 May-Jun; 54(3):9-14.
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  29. Polevoda BV, Gribanova LK, Ugarov VI, Lebedev AN, Tsoi TV. [Mapping of the regions participating in the replication, maintenance and mobilization of the R-plasmid pBS222 with a wide circle of bacterial hosts]. Genetika. 1988 Mar; 24(3):405-13.
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  30. Polevoda BV, Tsoi TV, Boronin AM. [Molecular genetic organization and origin of plasmid pBS52 with a broad range of bacterial hosts]. Genetika. 1987 Oct; 23(10):1823-31.
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  31. Polevoda BV, Tsoi TV, Boronin AM. [Structural-functional organization of R-plasmid pBS222 with a broad range of bacterial hosts]. Mol Gen Mikrobiol Virusol. 1986 Dec; (12):3-10.
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  32. Polevoda BV, Tsoi TV, Boronin AM. [Genetic characteristics and physical organization of the R-plasmid pBS52 with a broad range of bacterial hosts]. Mol Gen Mikrobiol Virusol. 1986 Nov; (11):18-23.
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  33. Anisimova LA, Viatkina GG, Polevoda BV, Korotiaev AI, Boronin AM. [Comparative study of non-conjugative R-plasmids from enterobacteria and Pseudomonas aeruginosa]. Mol Gen Mikrobiol Virusol. 1985 Jun; (6):24-8.
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  34. Stefanishin EE, Dekhtiarenko TD, Polishchuk LV, Polevoda BV. [Restriction analysis of hybrid plasmids pESO1-2 and pESG1-2]. Mikrobiol Zh. 1983 Mar-Apr; 45(2):40-3.
    View in: PubMed

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