PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities.
PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities.
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DOI：
10.1126/sciadv.adi2687
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发表时间：
2023-09-15
期刊：
影响因子：
13.6
通讯作者：
Ahel, Ivan
中科院分区：
文献类型：
--
作者：
Dukic, Nina;Stromland, Oyvind;Elsborg, Jonas Damgaard;Munnur, Deeksha;Zhu, Kang;Schuller, Marion;Chatrin, Chatrin;Kar, Pulak;Duma, Lena;Suyari, Osamu;Rack, Johannes Gregor Matthias;Baretic, Domagoj;Crudgington, Dorian Richard Kenneth;Groslambert, Josephine;Fowler, Gerissa;Wijngaarden, Sven;Prokhorova, Evgeniia;Rehwinkel, Jan;Schuler, Herwig;Filippov, Dmitri V.;Sanyal, Sumana;Ahel, Dragana;Nielsen, Michael L.;Smith, Rebecca;Ahel, Ivan
PARP 14是一种单ADP核糖基转移酶，参与免疫、转录和DNA复制应激管理的控制。然而，对PARP 14的ADP-核糖基化活性知之甚少，包括其底物特异性或PARP 14依赖的ADP-核糖基化如何逆转。我们表明，PARP 14是一种双功能酶，具有ADP-核糖基转移酶和水解酶活性，作用于蛋白质和核酸底物。特别是，我们表明，PARP 14宏结构域1是一个活跃的ADP-核糖基水解酶。我们还证明了PARP 9的第一个宏结构域的水解活性。我们揭示了具有失活的宏结构域1的PARP 14突变体的表达导致人细胞中蛋白质的单（ADP-核糖基）化显著增加，包括PARP 14本身和抗病毒PARP 13，并显示出特定的细胞表型。此外，我们证明了与SARS 2 Nsp 3密切相关的水解活性宏结构域Mac 1在体外和细胞中有效逆转PARP 14 ADP-核糖基化，支持病毒宏结构域的进化以抵消PARP 14介导的抗病毒反应。PARP 14是一种抗病毒PARP，其在一种多肽中组合了ADP-核糖基化写入器、读取器和擦除器功能。
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 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 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. PARP14 is an antiviral PARP that combines ADP-ribosylation writer, reader and eraser functions in one polypeptide.
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DOI：
10.3390/pathogens12050674
发表时间：
2023-05-03
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Delgado-Rodriguez SE;Ryan AP;Daugherty MD
通讯作者：
Daugherty MD
影响因子：
16
作者：
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通讯作者：
Ahel I
影响因子：
64.8
作者：
Ahel, Ivan;Ahel, Dragana;West, Stephen C.
通讯作者：
West, Stephen C.
影响因子：
4.4
作者：
Caprara, Greta;Prosperini, Elena;Natoli, Gioacchino
通讯作者：
Natoli, Gioacchino
影响因子：
16
作者：
Carraro, Massimo;Hendriks, Ivo A.;Hammond, Colin M.;Solis-Mezarino, Victor;Volker-Albert, Moritz;Elsborg, Jonas D.;Weisser, Melanie B.;Spanos, Christos;Montoya, Guillermo;Rappsilber, Juri;Imhof, Axel;Nielsen, Michael L.;Groth, Anja
通讯作者：
Groth, Anja