PXD055574

PXD055574 is an original dataset announced via ProteomeXchange.

Title	AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation
Description	Axis inhibition protein 1 (AXIN), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify AXIN acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN maintains the stability of IRF3 by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN undergoes a phase separation triggered by phosphorylated TBK1. This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN RGS domain, enhances the AXIN-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN agonist KYA1797K as an effective antiviral agent.
HostingRepository	PRIDE
AnnounceDate	2024-11-01
AnnouncementXML	Submission_2024-10-31_19:17:22.344.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	lele zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-05 00:31:10	ID requested
⏵ 1	2024-10-31 19:17:23	announced

10.1038/s41392-024-01978-y;

Dai DL, Xie C, Zhong LY, Liu SX, Zhang LL, Zhang H, Wu XP, Wu ZM, Kang K, Li Y, Sun YM, Xia TL, Zhang CS, Zhang A, Shi M, Sun C, Chen ML, Zhao GX, Bu GL, Liu YT, Huang KY, Zhao Z, Li SX, Zhang XY, Yuan YF, Wen SJ, Zhang L, Li BK, Zhong Q, Zeng MS, AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation. Signal Transduct Target Ther, 9(1):281(2024) [pubmed]

submitter keyword: Human, IRF3, AXIN1

Zeng Mu Sheng
contact affiliation	State Key Laboratory of Oncology in South China
contact email	zengmsh@sysucc.org.cn
lab head
lele zhang
contact affiliation	sysucc
contact email	1772391429@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055574
     1. Label: PRIDE project
     2. Name: AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation