Function and regulation of ARTD10-dependent mono-ADP-ribosylation in signaling and gene transcription

• Applicant: Professor Dr. Bernhard Lüscher
• Subject Area: Cell Biology ; Biochemistry
• Term: from 2013 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246008064

• Final Report Year: 2022

Final Report Abstract

Our effort to evaluate MARylation in the control of gene expression has not been successful until now. Whether MARylation is indeed not involved in transcription or whether our experiments were not of sufficient quality remains open at present. From reviewing the literature, there are quite a number of studies suggesting MARylation as a modification that affects chromatin and/or transcription. However, most studies provide indirect information and the mechanism of action is typically not resolved. Thus, the development of better reagents might allow addressing this question in the future. Most stimulating are the findings regarding RNA modification. Although this is early and preliminary information, RNA modification by MAR may well be of interest in different stress situations that is certainly worth studying in the future.

Publications

• 2020. Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins. Nature Communications 11, 5199
  Nowak K, Rosenthal F, Karlberg T, Bütepage M, Thorsell AG, Dreier B, Grossmann J, Sobek J, Imhof R, Lüscher B, Schüler H, Plückthun A, Leslie Pedrioli DM and Hottiger MO
  
• Comparative analysis of MACROD1, MACROD2 and TARG1 expression, localisation and interactome. Scientific Reports 10, 8286, 2020
  Žaja R, Aydin G, Lippok BE, Feederle R, Lüscher B and Feijs KLH
  
• 2021. ADP-ribosylation of RNA and DNA: from in vitro characterization to in vivo function. Nucleic Acids Research 49, 3634
  Weixler L, Schäringer K, Momoh J, Lüscher B, Feijs KLH and Žaja R
  
• 2021. ADP-ribosyltransferases, an update on function and nomenclature. FEBS Journal
  Lüscher B et al.
  
• 2021. Bacterial Growth Inhibition Screen (BGIS): harnessing recombinant protein toxicity for rapid and unbiased interrogation of protein function. FEBS Letters 595, 1422
  Guo H, Xu N, Prell M, Königs H, Hermanns-Sachweh B, Lüscher B, Kappes F
  
• 2021. Evaluation of 3- and 4-Phenoxybenzamides as Selective Inhibitors of the Mono-ADP-Ribosyltransferase PARP10. ChemistryOpen 10, 939
  Korn P, Classen A, Murthy S, Guareschi R, Maksimainen MM, Lippok BE, Galera-Prat A, Sowa ST, Voigt C, Rossetti G, Lehtiö L, Bolm C and Lüscher B
  
• 2021. Identification of a loss-of-function mutant via the Bacterial Growth Inhibition Screen (BGIS) reveals direct roles for DNA modulating activities of DEK in cellular chromatin. FEBS Letters 595, 1438
  Guo H, Prell H, Königs H, Xu N, Hermans-Sachweh B, Ferrando-May E, Lüscher B, Kappes F
  
• 2021. The search for inhibitors of macrodomains for targeting the readers and erasers of mono-ADP-ribosylation. Drug Discovery Today 26, 2547
  Fu W, Yao H, Bütepage M, Zhao Q, Lüscher B, Li J