2. Academic Validation
  3. Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system

Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system

  • EMBO J. 2025 May;44(10):2741-2773. doi: 10.1038/s44318-025-00421-4.
Rameez Raja 1,  Banhi Biswas 1,  Rachy Abraham 1,  Yiran Wang 1,  Che-Yuan Chang 1,  Ivo A Hendriks 2,  Sara C Buch-Larsen 2,  Hongrui Liu 1 3,  Xingyi Yang 1,  Chenyao Wang 4,  Hien Vu 1,  Anne Hamacher-Brady 1,  Danfeng Cai 1,  Anthony K L Leung 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • 2 NNF Center for Protein Research, Copenhagen N, DK-2200, Denmark.
  • 3 XDBio Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
  • 4 BeiGene Institute, Shanghai R&D Center, Shanghai, 200131, China.
  • 5 Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA. anthony.leung@jhu.edu.
  • 6 Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD, 21205, USA. anthony.leung@jhu.edu.
  • 7 McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. anthony.leung@jhu.edu.
  • 8 Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. anthony.leung@jhu.edu.
PMID: 40195501 DOI: 10.1038/s44318-025-00421-4
Abstract

Biomolecular condensates are cellular compartments without enveloping membranes, enabling them to dynamically adjust their composition in response to environmental changes through post-translational modifications. Recent work has revealed that interferon-induced ADP-ribosylation (ADPr), which can be reversed by a SARS-CoV-2-encoded hydrolase, is enriched within a condensate. However, the identity of the condensate and the responsible host ADP-ribosyltransferase remain elusive. Here, we demonstrate that interferon induces ADPr through transcriptional activation of PARP14, requiring both the physical presence and catalytic activity of PARP14 for condensate formation. Interferon-induced ADPr colocalizes with PARP14 and its associated E3 Ligase, DTX3L. These PARP14/ADPr condensates contain key components of p62 bodies-including the selective Autophagy receptor p62, its binding partner NBR1 and the associated protein TAX1BP1, along with K48-linked and K63-linked polyubiquitin chains-but lack the autophagosome marker LC3B. Knockdown of p62 disrupts the formation of these ADPr condensates. Importantly, these structures are unaffected by Autophagy inhibition, but depend on ubiquitination and Proteasome activity. Taken together, these findings demonstrate that interferon triggers PARP14-mediated ADP-ribosylation in p62 bodies, which requires an active ubiquitin-proteasome system.

Keywords

ADP-Ribosylation; Condensates; Interferon; Ubiquitin-Proteasome System; p62.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z