2. Academic Validation
  3. PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice

PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice

  • Cell Rep. 2025 Aug 26;44(8):116130. doi: 10.1016/j.celrep.2025.116130.
Jiashu Xu 1,  Tao Yu 2,  Zongwei Yue 3,  Xuan Lu 1,  Yandong Zhang 1,  Lei Wang 4,  Samaneh Shabani Åhrling 5,  Michael R Smith 2,  Yan Chun Li 4,  Jason Matthews 5,  Hening Lin 6
Affiliations

Affiliations

  • 1 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
  • 2 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • 3 Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
  • 4 Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
  • 5 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372 Oslo, Norway; Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
  • 6 Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA. Electronic address: linh1@uchicago.edu.
PMID: 40811059 DOI: 10.1016/j.celrep.2025.116130
Abstract

The regulation of type I interferon signaling is crucial for precisely tuning the innate immune response to combat pathogen invasions, fight Cancer, and prevent autoimmune diseases. PARP7, a mono-ADP-ribosyltransferase also called TiPARP (tetrachlorodibenzo-p-dioxin [TCDD]-inducible PARP), is reported to inhibit the production of type I interferons. Here, we find that PARP7 suppresses type I interferon signaling instead of interferon production. PARP7 ADP-ribosylates and promotes the ubiquitination of signal transducer and activator of transcription 1 (STAT1) and STAT2, which recruits p62 to promote the degradation of STAT1 and STAT2 through Autophagy. By reducing STAT1 and STAT2 levels, PARP7 decreases type I interferon signaling. We further show that the inhibition of PARP7 promotes type I interferon signaling and relieves experimental autoimmune encephalomyelitis (EAE) symptoms in mice. Our findings revealed a molecular mechanism via which PARP7 suppresses type I interferon signaling, offering insights into the immune-modulatory function of PARP7 and suggesting PARP7 inhibition as a potential treatment strategy for multiple sclerosis.

Keywords

ADP-ribosylation; CP: Molecular biology; CP: Neuroscience; EAE; PARP7; STAT1; STAT2; TiPARP; autophagy; multiple sclerosis; type I interferon signaling; ubiquitination.

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