TY - JOUR
T1 - PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities
AU - Dukić, Nina
AU - Strømland, Øyvind
AU - Elsborg, Jonas Damgaard
AU - Munnur, Deeksha
AU - Zhu, Kang
AU - Schuller, Marion
AU - Chatrin, Chatrin
AU - Kar, Pulak
AU - Duma, Lena
AU - Suyari, Osamu
AU - Rack, Johannes Gregor Matthias
AU - Baretić, Domagoj
AU - Crudgington, Dorian Richard Kenneth
AU - Groslambert, Joséphine
AU - Fowler, Gerissa
AU - Wijngaarden, Sven
AU - Prokhorova, Evgeniia
AU - Rehwinkel, Jan
AU - Schüler, Herwig
AU - Filippov, Dmitri V.
AU - Sanyal, Sumana
AU - Ahel, Dragana
AU - Nielsen, Michael L.
AU - Smith, Rebecca
AU - Ahel, Ivan
N1 - Publisher Copyright:
Copyright © 2023 The Authors.
PY - 2023
Y1 - 2023
N2 - PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dualfunction enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.
AB - PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dualfunction enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.
UR - https://www.scopus.com/pages/publications/85171240255
U2 - 10.1126/sciadv.adi2687
DO - 10.1126/sciadv.adi2687
M3 - 文章
C2 - 37703374
AN - SCOPUS:85171240255
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 37
M1 - eadi2687
ER -