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PARP14 is a PARP with both ADP-ribosyl transferase 1 and hydrolase activities

ABSTRACT: 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. Here we show that PARP14 is dual function 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 dramatic increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13. 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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Jonas Elsborg

LAB HEAD: Michael Lund

PROVIDER: PXD043452 | Pride | 2023-08-14

REPOSITORIES: Pride

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			Action	DRS
	20230613_EXPL7_LC4_JE_collab_ND-Ahel_P14_MD1_af1521_01.raw	Raw
	20230613_EXPL7_LC4_JE_collab_ND-Ahel_P14_MD1_af1521_02.raw	Raw
	20230613_EXPL7_LC4_JE_collab_ND-Ahel_P14_MD1_af1521_03.raw	Raw
	20230613_EXPL7_LC4_JE_collab_ND-Ahel_P14_MD1_af1521_04.raw	Raw
	20230613_EXPL7_LC4_JE_collab_ND-Ahel_P14_MD1_af1521_05.raw	Raw

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A study into the ADP-ribosylome of IFN--stimulated THP-1 human macrophage-like cells identifies ARTD8/PARP14 and ARTD9/PARP9 ADP-ribosylation

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