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Thomas Arnesen

forsker, forskergruppe leder

Protein N-terminal acetylering - Fra molekylære mekanismer til sykdom

Molekylærbiologisk institutt

METASIG: Proteinmodifisering og cellulær signalisering

Hjemmeside: http://www.uib.no/rg/nat

Stilling: forsker, forskergruppe leder

Telefon: 55 58 45 28

E-post:

Besøksadresse: HIB - Thormøhlensgt. 55

Protein modifications with an emphasis on protein N-terminal acetylation

Cellular signaling

Development of anticancer drugs

2012-> Researcher/Group leader (Bergen Research Foundation BFS)

Department of Molecular Biology, University of Bergen.

 

2010-> Researcher

Department of Surgery, Haukeland University Hospital

 

2010-2013 Researcher/Principal Investigator (Research Council of Norway)                                                                                                                                                                                                                                                  University of Bergen, Norway

 

2009-2009 Associate Professor                                                                                                                                                                                                                                                                                                                                                    University of Bergen, Norway

 

2006-2009 Post Doc (Norwegian Health Authorities West)                                                                                                                                                                                                                                                                   University of Bergen, Norway (Prof. JE Varhaug and Prof. JR Lillehaug) and                                                                                                                                                                                                                                                             University of Rochester, USA (Prof. Fred Sherman)

 

2006 Ph.D. Molecular Biology (Norwegian Cancer Society)                                                                                                                                                                                                                                                                     University of Bergen, Norway (Prof. JE Varhaug and Prof. JR Lillehaug)

 

2002 Cand. scient. (M.Sc.) Molecular Biology                                                                                                                                                                                                                                                                                       University of Bergen, Norway  (Prof. AM Szilvay)

 

1999 Biomedical Laboratory Scientist (B.Sc.)                                                                                                                                                                                                                                                                                         Bergen University College, Norway

Publikasjoner i Cristin

Scientific publications (peer reviewed)

Arnesen T, Anderson D, Baldersheim C, Lanotte M, Varhaug JE, Lillehaug JR. (2005) Identification and characterization of the human ARD1-NATH protein acetyltransferase complex. Biochemical J 386(Pt 3):433-43.

 

Furnes C, Arnesen T, Askjaer P, Kjems J, Szilvay AM. (2005) HIV-1 Rev oligomerization is not obligatory in the presence of an extra basic domain. Retrovirology 2(1):39.

 

Arnesen T, Gromyko D, Horvli O, Fluge Ø, Lillehaug JR, Varhaug JE (2005) Expression of NATH and hARD1 proteins in thyroid neoplasms. Thyroid 15(10):1131-6.

 

Arnesen T, Kong X, Evjenth R, Gromyko D, Varhaug JE, Lin Z, Sang N, Caro J, Lillehaug JR. (2005) Interaction between HIF-1α (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1α. FEBS Lett 579(28):6428-32.

 

Arnesen T, Anderson D, Torsvik J, Varhaug JE, Lillehaug JR. (2006) Cloning and characterization of hNAT5/hSAN: An evolutionary conserved component of the NatA protein N-α-acetyltransferase complex. Gene 371:291-295.

Arnesen T, Gromyko D, Pendino F, Ryningen A, Varhaug JE, Lillehaug JR. (2006) Induction of apoptosis in human cells by RNAi mediated knock-down of hARD1 and NATH, components of the protein N-α-acetyltransferase complex. Oncogene 25:4350-4360.

 

Arnesen T. (2006) HIF-1α and ARD1: enemies, friends or neither? Nat Rev Cancer. 6 (3): doi:10.1038/nrc1779-c1.

 

Arnesen T, Betts M, Pendino F, Liberles D, Anderson D, Caro J, Kong X, Varhaug JE, Lillehaug JR. (2006) Characterization of hARD2, a processed hARD1 gene duplicate encoding a human protein N-α-acetyltransferase. BMC Biochem 7:13.

 

Knappskog S, Geisler J, Arnesen T, Lillehaug JR, Lønning PE. (2006) A novel type of deletion in the CDKN2A gene identified in a melanoma-prone family. Genes Chr. Cancer. 45(12):1155-63.

 

Starheim K, Arnesen T, Gromyko D, Ryningen A, Varhaug JE, Lillehaug JR. (2008) Identification of the human Na-acetyltransferase complex B (hNatB) – a complex important for cell cycle progression. Biochemical J 415:325-331.

 

Arnesen T, Thompson PR, Varhaug JE, Lillehaug JR. (2008) The protein acetyltransferase ARD1 – a novel cancer drug target? Curr Cancer Drug Targets. 8:545-553.

 

Målen H, Lillehaug JR, Arnesen T. (2009) The protein Nα-terminal acetyltransferase hNaa10p (hArd1) is phosphorylated in HEK293 cells. BMC Res Notes 2:32.

Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, Varhaug JE, Vandekerckhove J, Lillehaug JR, Sherman F, Gevaert K. (2009) Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc Natl Acad Sci USA. 106:8157-8162.

 

Starheim K, Gromyko D, Ryningen A, Varhaug JE, Lillehaug JR, Arnesen T. (2009) Knockdown of the human NatC protein Nα-terminal acetyltransferase complex induces p53-mediated apoptosis and aberrant hArl8b localization. Mol Cell Biol 29(13):3569-81.

 

Arnesen T, Gromyko D, Kagabo D, Betts MJ, Varhaug JE, Anderson D, Lillehaug JR. (2009) A novel human NatA Nα-terminal acetyltransferase complex: hNaa16p-hNaa10p (hNat2-hArd1). BMC Biochem. 10:15.

 

Takubo K, Tsuchiya H, Kurimasa A, Arnesen T, Ryoke K, Shiota G. (2009) Involvement of N-acetyltransferase human in the cytotoxic activity of 5-fluorouracil. Anti-Cancer Drugs. 20:668-75.

Arnesen T. (2009) Protein N-terminal acetylation: NAT 2007–2008 Symposia. BMC Proc. 3 (Suppl 6):S1.

 

Polevoda B, Arnesen T, Sherman F. (2009) A synopsis of eukaryotic Nα-terminal acetyltransferases: nomenclature, subunits and substrates. BMC Proc. 3 (Suppl 6):S2.

 

Starheim KK, Gromyko D, Velde R, Varhaug JE, Arnesen T. (2009) Composition and biological significance of the human Nα-terminal acetyltransferases. BMC Proc. 3 (Suppl 6):S3

 

Evjenth R, Hole K, Karlsen OA, Ziegler M, Arnesen T, Lillehaug JR (2009) Human Naa50 (Nat5/San) displays both protein N-alpha and N-epsilon acetyltransferase activity. J Biol Chem. 284(45):31122-9.

 

Arnesen T, Starheim KK, Van Damme P, Evjenth R, Dinh H, Betts M, Ryningen A, Vandekerckhove J, Gevaert K, Anderson D. (2010) The chaperone-like protein HYPK acts together with NatA in cotranslational N-terminal acetylation and prevention of Huntingtin aggregation. Mol Cell Biol 30(8):1898-909.

 

Gromyko D, Arnesen T, Ryningen A, Varhaug JE, Lillehaug JR (2010) Depletion of the human N-terminal acetyltransferase A (hNatA) induces p53-dependent apoptosis and p53-independent growth inhibition. Int J Cancer 127(12):2777-89.

 

Van Damme P, Evjenth R, Foyn H, Demeyer K, De Bock P-J, Lillehaug JR, Vandekerckhove J, Arnesen T, Gevaert K. (2011) Proteome-derived peptide libraries allow detailed analysis of the substrate specificities of Nα-acetyltransferases and point to hNaa10p as the posttranslational actin Nα-acetyltransferase. Mol Cell Proteomics 10: M110.004580.

 

Helsens K, Van Damme P, Degroeve S, Martens L, Arnesen T, Vandekerckhove J, Gevaert K. (2011) Bioinformatics analysis of a Saccharomyces cerevisiae N-terminal proteome provides evidence of alternative translation initiation and post-translational N-terminal acetylation. J Proteome Res 10(8):3578-3589.

 

Arnesen T. (2011) Towards a functional understanding of protein N-terminal acetylation. PLoS Biology 9(5): e1001074.

 

Rope A, Wang K, Evjenth R, Xing J, Johnston JJ, Swensen JJ, Johnson WE, Moore B, Huff CD, Bird LM, Carey JC, Opitz JM, Stevens CA, Jiang T, Schank C, Fain HD, Robison R, Dalley B, Chin S, South ST, Pysher TJ, Jorde LB, Hakonarson H, Lillehaug JR, Biesecker LB, Yandell M, Arnesen T, Lyon GJ (2011) Using VAAST to Identify an X-Linked Disorder Resulting in Lethality in Male Infants Due to N-Terminal Acetyltransferase Deficiency. Am J Hum Genet 89(1):28-43. Comment in Nature News: doi:10.1038/news.2011.382

 

Van Damme P, Arnesen T, Gevaert K (2011) Protein alpha-N-acetylation studied by N-terminomics. FEBS J 278(20):3822-34.

 

Van Damme P, Hole K, Pimenta-Marques A, Helsens K, Vandekerckhove J, Martinho RG, Gevaert K, Arnesen T (2011) NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation. PLoS Genet 7(7): e1002169.

 

Hole K, Van Damme P, Dalva M, Aksnes H, Glomnes N, Varhaug J, Lillehaug JR, Gevaert K, Arnesen T (2011) The human N-alpha-acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4. PLoS ONE 6(9): e24713.

 

Liszczak G, Arnesen T, Marmorstein R (2011) Structure of a ternary Naa50p (NAT5/San) Nα-terminal Acetyltransferase complex reveals the molecular basis for substrate specific acetylation. J Biol Chem 286(42):37002-10.

 

Evjenth R, Brenner A, Thompson PR, Arnesen T, Frøystein NÅ, Lillehaug JR (2012) The human protein N-terminal acetyltransferase hNaa50p (hNat5/hSan) follows an ordered sequential catalytic mechanism: A combined kinetic and NMR study. J Biol Chem 287(13):10081-8.

 

Starheim KK, Gevaert K, Arnesen T (2012) Protein N-terminal acetyltransferases: when the start matters. Trends Biochem Sci 37(4):152-61.

 

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 (2012) N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci USA 109(31):12449-54.

 

Grauffel C, Abboud A, Liszczak G, Marmorstein R, Arnesen T, Reuter N (2012) Specificity and Versatility of Substrate Binding Sites in Four Catalytic Domains of Human N-Terminal Acetyltransferases. PLoS ONE 7(12): e52642

 

Kalvik TV and Arnesen T (2013) Protein N-terminal acetyltransferases in cancer. Oncogene 32(3):269-76.

 

Foyn H, Van Damme P, Støve S, Glomnes N, Evjenth R, Gevaert K, Arnesen T (2013) Protein N-Terminal acetyltransferases act as N-Terminal propionyltransferases in vitro and in vivo. Mol Cell Proteomics 12:42-54. Covered by ASBMB news.

 

Van Damme P, Arnesen T, Ruttens B, Gevaert K (2013) In-gel N-acetylation for the Quantification of the Degree of Protein in vivo N-terminal Acetylation. Methods Mol Biol 981:115-26.

 

Evjenth R, Van Damme P, Gevaert K, Arnesen T (2013) HPLC-based Quantification of in vitro N-terminal Acetylation. Methods Mol Biol 981:95-102.

 

Foyn H, Jones JE, Lewallen D, Narawane R, Varhaug JE, Thompson PR, Arnesen T (2013) Design, Synthesis, and Kinetic Characterization of Protein N-Terminal Acetyltransferase Inhibitors. ACS Chem Biol 8:1121–1127.

 

Aksnes H, Osberg C, Arnesen T (2013) N-Terminal Acetylation by NatC Is Not a General Determinant for Substrate Subcellular Localization in Saccharomyces cerevisiae. PLOS ONE 8(4): e61012.

 

Arnesen T, Glomnes N, Strømsøy S, Knappskog S, Heie A, Akslen LA, Grytaas M, Varhaug JE, Gimm O, Brauckhoff M (2013) Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population based study from Western Norway. Langenbecks Arch Surg 398(6):869-74.

 

Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R (2013) Molecular basis for N-terminal acetylation by the heterodimeric NatA complex. Nature Struct Mol Biol in press

 

Dutta RK, Welander J, Brauckhoff M, Arnesen T, Alesina P, Walz M, Söderkvist P, Gimm O (2014) Complementary somatic mutations in sporadic aldosterone producing adrenal adenomas Endocr Relat Cancer ERC in press

 

Van Damme P, Støve SI, Glomnes N, Gevaert K, Arnesen T (2014) A Saccharomyces cerevisiae model reveals in vivo functional impairment of the Ogden syndrome N-terminal acetyltransferase Naa10S37P mutant. Mol Cell Proteomics in press.

-Human protein N-terminal acetyltransferases (NATs):

identification, substrate specificities, biological importance, molecular mechanisms.

-Development of NAT inhibitors