Syvn1-flox Mouse

SYVN1, also known as synoviolin 1, is an E3 ubiquitin ligase. Ubiquitination is a crucial process in cells that can regulate protein function, localization, and degradation. SYVN1 participates in multiple cellular pathways and is of great biological importance in processes such as inflammation, cell death, and tumor metastasis [1,2].

In Gasdermin D (GSDMD)-mediated pyroptosis, SYVN1 deficiency inhibits pyroptosis, LDH release, and PI uptake. SYVN1 directly interacts with GSDMD, mediating K27-linked polyubiquitination of GSDMD on specific residues, thus promoting GSDMD-induced pyroptotic cell death [1].

In hepatocellular carcinoma (HCC), high expression of SYVN1 is related to tumor metastasis. Interference with SYVN1 expression in hepatoma cell lines affects their growth, migration, and invasion ability [2].

In osteoarthritis, the LncRNA SNHG7/miR-34a-5p/SYVN1 axis plays a role in cell proliferation, apoptosis, and autophagy. Down-regulation of SYVN1 was observed in OA tissues and cells [3].

In spinal cord ischemia-reperfusion injury, SYVN1 overexpression inhibits ferroptosis of neurons in rats by regulating the HMGB1/NRF2/HO-1 axis [4].

In pancreatic cancer, the SLC35F2-SYVN1-TRIM59 axis regulates ferroptosis by inhibiting endogenous p53 [5].

In lung adenocarcinoma, SYVN1-mediated ubiquitylation of MCT4 promotes its localization in the plasma membrane, facilitating lactate export and tumor progression [6].

In spinal cord injury, Syvn1 suppresses neuronal ferroptosis by activating the Stat3/Gpx4 axis [7].

In retinopathy of prematurity, SYVN1 overexpression promotes ubiquitination and degradation of STAT3, preventing neovascularization [8].

In diabetic cardiomyopathy, exogenous H2S promotes ubiquitin-mediated degradation of SREBP1 via SYVN1 S-sulfhydration to alleviate the disease [9].

In sepsis-induced liver injury, IGF2BP3 modifies GLI2 to transcriptionally regulate SYVN1, which then inhibits PPARα-mediated autophagy and exacerbates liver injury [10].

In conclusion, SYVN1 is a key E3 ubiquitin ligase involved in various biological processes. Studies using gene-knockout or conditional-knockout mouse models (or cell models with SYVN1 expression interference) have revealed its role in diseases such as inflammation-related diseases, cancer, neurodegenerative-like diseases, and metabolic diseases. These findings provide potential therapeutic targets for these diseases.