Ask about this productRelated genes to: Kimmy-1 Tollip
- Gene:
- TOLLIP NIH gene
- Name:
- toll interacting protein
- Previous symbol:
- -
- Synonyms:
- IL-1RAcPIP
- Chromosome:
- 11p15.5
- Locus Type:
- gene with protein product
- Date approved:
- 2003-03-13
- Date modifiied:
- 2016-10-05
Related products to: Kimmy-1 Tollip
Related articles to: Kimmy-1 Tollip
- - Source: PubMed
Publication date: 2026/07/31
Huang KeShi YuLin JiajieQin ChengyiQin ChangshuaiLu XianzheLan Changgong - Metabolic reprogramming toward aerobic glycolysis is increasingly recognized as a key mechanism in the pathogenesis of psoriasis, but the underlying regulatory mechanisms remain unclear. Here, we identify Toll-interacting protein (TOLLIP) as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. We found that TOLLIP is significantly upregulated in psoriatic lesions, and its genetic deletion in mice exacerbated disease severity in imiquimod (IMQ)-induced psoriasis models. Mechanistically, TOLLIP interacts with the rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) via its coupling of ubiquitin to ER degradation (CUE) domain (179-274 aa), inhibits PKM2's metabolic enzyme activity and attenuates aerobic glycolysis, thereby mitigating keratinocyte hyperproliferation and inflammation. Therapeutic delivery of Tollip or Tollip (179-274 aa) via adeno-associated virus (AAV) vectors ameliorated psoriasis progression in mice. Our findings establish the TOLLIP-PKM2-glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target. - Source: PubMed
Publication date: 2026/07/31
Jiang XiuhuanMiao GuoyingShen NaHan QingxiaHan XiaoruQiao ZichangFeng KexinTan ZhuoWang YaguangLiu XiuhuaWu ChenYan Zhenzhen - The emergence of swine acute diarrhea syndrome coronavirus (SADS-CoV), an alpha-coronavirus that causes fatal enteric disease in neonatal piglets with mortality rates up to 90%, demonstrates that bat-origin coronavirus has expanded its host range to pigs. Although SADS-CoV exhibits significant pandemic potential and capacity for cross-species transmission, the replication mechanisms of SADS-CoV remain largely unexplored. Identifying host factors responsible for SADS-CoV replication and elucidating its underlying mechanisms is essential for advancing fundamental knowledge of coronavirus biology and developing antiviral therapies. Here, we identified PABPC1 as a novel interactor of the SADS-CoV nucleocapsid (N) protein. Overexpression of PABPC1 restricted SADS-CoV infection, whereas knockdown of PABPC1 enhanced viral replication. Further study indicated PABPC1 as a host restriction factor of SADS-CoV in a manner dependent on its PABC domain. Mechanistically, PABPC1 enhances the ubiquitination of the N protein, therefore facilitating its recognition by the cargo receptor TOLLIP for selective autophagic degradation. This study systematically analyzes the interaction of host factors and the SADS-CoV N protein and identifies PABPC1 as a host restriction factor that limits viral replication via TOLLIP-mediated selective autophagy degradation of the N protein. These findings expand our knowledge of the SADS-CoV replication mechanism and provide additional antiviral strategies for controlling SADS-CoV. - Source: PubMed
Publication date: 2026/07/17
Sun MaowenYuan CongZhang YuZhu XueliangShi LeiDuan YueyueMao WenquanLi LuyaoLiu YangheWang Qi - Porcine epidemic diarrhea virus (PEDV) is a devastating enteric pathogen in neonatal piglets, causing outbreaks with high mortality. The lack of effective vaccines or treatments makes elucidating host-pathogen interactions essential for developing control strategies. In this study, we identify phosphoenolpyruvate carboxykinase 2 (PCK2) as a host restriction factor that targets the viral nucleocapsid (N) protein for degradation, thereby suppressing PEDV replication. This PCK2-mediated antiviral effect was reversed by autophagy inhibitors, indicating the involvement of a selective autophagic. Mechanistically, we found that PCK2, the N protein, the E3 ubiquitin ligase Traf6, and the cargo receptor Tollip form a functional complex. Depletion of either Traf6 or Tollip disrupted the autophagy pathway, restored N protein stability, and consequently rescued viral replication from PCK2 inhibition. This study unveils a novel antiviral mechanism in which PCK2 orchestrates the selective autophagic degradation of the PEDV N protein, highlighting the PCK2-Traf6-Tollip axis as a promising therapeutic direction. - Source: PubMed
Gao AoYang XinyuQin WenzhenZheng DongfangLiu YuchangSun HeChen ZongyanTong GuangzhiXue ShuangKong NingZheng Lanlan - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs sophisticated strategies to subvert host innate immunity, a critical determinant of viral establishment and dissemination. Nevertheless, the immunomodulatory functions of coronavirus structural proteins remain incompletely understood. Here, we identify the evolutionarily conserved membrane (M) protein of SARS-CoV-2 as an innate immune antagonist that suppresses nuclear factor kappa-B (NF-κB) activation. Functional assays revealed that the M protein markedly inhibited NF-κB activation and reduced proinflammatory cytokine production in vitro. In lung epithelial M-expressing mouse, M significantly attenuated LPS-induced inflammation. Mechanistically, M protein from diverse coronaviruses directly interacts with host Toll-interacting protein (TOLLIP), stabilizing TOLLIP‒IRAK1 complex, preventing IRAK1 activation, thereby suppressing downstream NF-κB signaling and creating a permissive cellular microenvironment for viral replication. We mapped a conserved linker region within the M protein as the core motif mediating this interaction. This binding is highly conserved across coronaviruses, highlighting the fundamental role of the M-TOLLIP axis in viral immune evasion. Our findings reveal a conserved pan-coronavirus immune evasion strategy by which coronaviruses target TOLLIP to subvert Toll-like receptor (TLR)-NF-κB signaling. The conserved M-linker region thus represents a potential broad-spectrum antiviral target, providing a structural framework for developing next-generation antivirals against current and emerging coronavirus threats. - Source: PubMed
Publication date: 2026/06/17
Zhang YabinKang LuZhong YuShao SongjunXue SenrenLiu ChangliangZheng XiaoqiLin Jing-WenChen YuLuo FengmingWan Huajing