Products Cited in Publications Worldwide PARP7 inhibition stabilizes STAT1/STAT2 and relieves experimental autoimmune encephalomyelitis in mice

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

Xu, Jiashu; Yu, Tao; Yue, Zongwei; Lu, Xuan; Zhang, Yandong; Wang, Lei; Åhrling, Samaneh Shabani; Smith, Michael R; Li, Yan Chun; Matthews, Jason

DOI: PMID:

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.

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RBN-2397

A13292212381037-82-598%

RBN-2397

286.0/50mg

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