Modifications and targeting of protein termini Part B

Professor Thomas Arnesen received his Ph.D. in molecular biology from the University of Bergen, Norway in 2006. After postdoctoral work at Haukeland University Hospital and University of Rochester Medical Center, he established his own lab at the University of Bergen in 2010. His main interest has been protein N-terminal acetylation and the responsible enzymes, the N-terminal acetyltransferases (NATs). Using Saccharomyces cerevisiae and human cell models combined with in vitro approaches his lab and collaborators have i) identified and defined the presumed complete cytosolic human NAT-machinery including NATs acting post-translationally, ii) quantitatively analysed the N-terminal acetylomes of yeast and human cells, iii) developed novel assays for NAT-profiling, iv) gained mechanistic insights of the molecular and cellular effects of N-terminal acetylation, v) contributed to the understanding of the physiological and clinical importance of NATs by revealing the links between NatA and cancer cell survival and drug sensitisation, and lately by defining genetic disorders caused by pathogenic NAT variants. The Arnesen lab also contributed to solving the first NAT-structures and developing the first potent NAT-inhibitors. With Fred Sherman and Bogdan Polevoda, Arnesen introduced the NAA (N-alpha acetyltransferase) nomenclature of the N-terminal acetyltransferase genes and proteins, and he acts as the specialist advisor for the HUGO Gene Nomenclature Committee for these genes. Arnesen is one of the founders and council members of the International Society of Protein Termini (ISPT). He has organized several symposia on N-terminal acetylation, and in 2022 he was the head organizer of the EMBO Workshop ‘Protein Termini – From mechanism to biological impact’ in Bergen, Norway. Arnesen has co-authored more than 100 peer-reviewed publications. Today he is head of the Translational Cell Signaling and Metabolism group at the Dept. of Biomedicine, UiB, supported by the Research Council of Norway and ERC. Here his team continues the basic and translational research to understand the impact of protein N-terminal modifications.

1. In vitro production of N-degron fused proteins and its applicationHyun Kyu Song, Bong Heon Kim, Leehyeon Kim, Do Hoon Kwon and Woo Seok Yang2. Identification of N-degrons and N-recognins using peptide pull-downs combined with quantitative mass spectrometry-based proteomicsFranziska Müller and Tanja Bange3. Monitoring ADO-dependent proteolysis in cells using fluorescent reporter proteinsThomas P. Keeley4. Monitoring the interactions between N-degrons and N-recognins of the Arg/N-degron pathwayYong Tae Kwon, Ah Jung Heo, Soon Chul Kwon and Jihoon Lee5. Characterization and chemical modulation of p62/SQSTM1/Sequestosome-1 as an autophagic N-recognin of the Arg/N-degron pathwaySu Jin Lee, Hye Yeon Kim, Min Ju Lee, Su Bin Kim, Yong Tae Kwon and Chang Hoon Ji6. Characterization of degradation signals at protein C-terminiHsueh-Chi S. Yen, Chi-Wei Yeh, Wei-Chieh Huang, Shu-Yu Hsu, Ching-Yu Chu and Lo-Tung Lee7. Analysis of higher plant N-degron pathway components and substrates via expression in S. cerevisiaeJessica Böhm, Nikola Winter, Aida Kozlic, Theresia Telser, Lilian Nehlin and Andreas Bachmair8. Building libraries to dissect terminal degrons with fluorescent timersAnton Khmelinskii, Ka-Yiu Edwin Kong, Christian Reinbold and Michael Knop9. Affinity isolation and biochemical characterisation of N-degron ligands using the N-recognin, ClpSKaye N. Truscott and David A. Dougan10. Probing the effects of N-terminal acetylation on a-synuclein structure, aggregation and toxicityJanet R. Kumita, Rosie Bell and Michele Vendruscolo11. Increasing the coverage of the N-terminome with Lys-N Amino Terminal enrichment (LATE)Oded Kleifeld, Rawad Hanna, Andrey Rozenberg and Tali Lavy12. In vitro autoubiquitination activity of E3 ubiquitin ligases of the N-degron pathwayNico Dissmeyer13. Antibodies specific for N-terminal arginylationNico Dissmeyer14. TEV protease cleavage in generation of artificial substrate proteins bearing neo-N-terminiNico Dissmeyer and Lioba Inken Winckler15. Multiplexed protein stability (MPS) profiling of terminal degrons using fluorescent timer libraries in Saccharomyces cerevisiaeMichael Knop, Christian Reinbold, Ka-Yiu Edwin Kong, Ilia Kats and Anton Khmelinskii16. Using cell lysates to assess N-terminal acetyltransferase activity and impairmentThomas Arnesen, Nina McTiernan and Malin Lundekvam