Ask about this productRelated genes to: SYVN1 antibody
- Gene:
- SYVN1 NIH gene
- Name:
- synoviolin 1
- Previous symbol:
- -
- Synonyms:
- HRD1, DER3
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-07-28
- Date modifiied:
- 2016-06-21
Related products to: SYVN1 antibody
Related articles to: SYVN1 antibody
- Lung cancer remains one of the most lethal and prevalent malignancies worldwide. Although E3 ubiquitin ligase SYVN1 is frequently amplified in lung cancer, its functional role has not been fully elucidated. This study investigates the mechanistic involvement of SYVN1 in regulating the GATA3/NRP1 axis in A549 cells to provide novel insights into potential therapeutic strategies for lung cancer. Expression levels of SYVN1 were assessed in BEAS-2B, A549, NCI-H647, NCI-H2170, and NCI-H520, NCI-H69 cells. Functional assays were conducted after overexpressing or silencing SYVN1, GATA3, and/or NRP1 in A549 cells to examine their interdependent roles. The cells' proliferation, wound healing, invasion and migration abilities were evaluated through CCK-8, scratch assay and Transwell assays, respectively. The results indicated that SYVN1 was upregulated in A549 cells and significantly promoted cell proliferation, invasion, and migration. Mechanistically, SYVN1 interacted with GATA3 and regulated its ubiquitination. Knockdown of SYVN1 suppressed A549 cell proliferation, wound healing, invasion, and migration, and these effects could be reversed by overexpressing GATA3. Similarly, silencing GATA3 reduced these malignant characteristics, but these effects could be restored by overexpressing NRP1, and the knockdown of NRP1 could abrogate the tumor-promoting effects of SYVN1 overexpression. SYVN1 overexpression counteracted the inhibitory effects of NRP1 silencing on A549 tumor progression. Taken together, all these findings prove that SYVN1 could promote the malignant characteristics of A549 cells by modulating the GATA3/NRP1 axis. Thus, targeting SYVN1 could represent a promising therapeutic approach for treating lung cancer. - Source: PubMed
Publication date: 2026/08/18
Wang ShanLu SuliWang ZhenXuan GuipingTan Jianhua - Serine hydroxymethyltransferase 2 (SHMT2) is a key mitochondrial enzyme involved in one-carbon metabolism, but its regulation and functional significance in acute kidney injury (AKI) remain unclear. To determine whether SHMT2 downregulation contributes to tubular injury and to elucidate the underlying molecular mechanism, we established murine models of AKI induced by ischemia-reperfusion injury and unilateral ureteral obstruction. In parallel, human proximal tubular HK-2 cells were exposed to hypoxia/reoxygenation or transforming growth factor-β1 stimulation in vitro. We found that SHMT2 expression was markedly reduced in renal tubular epithelial cells across both murine AKI models, showing a significant inverse association with the severity of tubular injury. To elucidate the underlying mechanisms, we subsequently utilized genetic (shRNA) and pharmacological (SHIN1) inhibition of SHMT2, alongside overexpression of the E3 ubiquitin ligase synoviolin (SYVN1). Functional inhibition of SHMT2 aggravated tubular epithelial damage by inducing mitochondrial dysfunction, increasing oxidative stress, promoting the accumulation of nephrotoxic uremic toxins, and impairing both glycolysis and oxidative phosphorylation. Mechanistically, under AKI conditions, elevated SYVN1 directly interacted with SHMT2 via its conserved RING domain, promoting K48-linked polyubiquitination and subsequent proteasomal degradation of SHMT2. Ultimately, this ubiquitin-dependent degradation of SHMT2, mediated by SYVN1, drives AKI progression by inducing metabolic reprogramming and bioenergetic failure in renal tubular cells. These findings highlight the SYVN1/SHMT2 axis as a novel pathogenic mechanism and a promising therapeutic target for preserving tubular metabolic homeostasis and alleviating kidney injury. - Source: PubMed
Publication date: 2026/08/06
Li Sha-ShaChen XiZhang QiTang JingYu Li-XiaLiu Qi-Feng - Mitochondrial transport and distribution are crucial for cellular homeostasis, yet whether and how they are regulated by endoplasmic reticulum (ER)-mitochondria contact sites remains unclear. Here, we demonstrate that the ER protein atlastin-2 (ATL2) orchestrates mitochondrial transport and distribution by promoting assembly of the transport machinery at ER-mitochondria contact sites. Mechanistically, ATL2 recruits the adaptor trafficking kinesin-binding protein 1 (TRAK1) to the ER membrane, strengthening the interaction of TRAK1 with the mitochondrial transport adaptor MIRO1 to promote anterograde mitochondrial transport. Loss of ATL2 disrupts this process, leading to perinuclear mitochondrial clustering. We further find that ATL2 stabilizes ER-mitochondria contact sites by interacting with MFN2, providing a platform for mitochondrial transport complex assembly. Moreover, in hypoxia, ATL2 is ubiquitinated at lysine 567 by the E3 ligase SYVN1, leading to its degradation and a resulting defect in mitochondrial distribution. Our findings elucidate a novel ER-mediated mechanism for mitochondrial transport. - Source: PubMed
Publication date: 2026/07/30
Cheng YiruChai PeiyuanPei XiayuheChen YiwenHuang XiaoshuaiLiu BeiWu YiqianTeng JunlinZheng PengliChen Jianguo - Targeted protein degradation (TPD) via proteolysis-targeting chimeras (PROTACs) is a powerful therapeutic strategy, yet only a small fraction of the >600 human E3 ligases have been harnessed. To expand this repertoire, we developed clickable photoaffinity probes based on clinically used drugs and metabolites to identify potential E3 ligases as targets. Here, we report the discovery of clofibric acid with a molecular weight of only 214 Da as a ligand for synoviolin (SYVN1). We demonstrate its utility by developing clofibric acid-based BRD4 PROTACs. The linker length and architecture play a critical role in the target degradation efficiency. The clofibric acid-derived BRD4 PROTACs achieve selective BRD4 degradation in an SYVN1-dependent manner. Our findings establish clofibric acid as a robust addition to the TPD toolbox, offering a novel E3 ligase recruitment strategy for the development of next-generation degraders. - Source: PubMed
Publication date: 2026/06/06
Warren JuliaMunakala AnandaraoZientek Keith DKim KilsunWilmarth Phillip AReddy Ashok PLi Bingbing XXiao Xiangshu - We applied the TempO-LINC® platform to generate single-cell transcriptomic (SCTr) profiles of ∼40,000 HepaRG cells exposed to etoposide, brefeldin A, cycloheximide, rotenone, tBHQ, troglitazone, and tunicamycin at three concentrations for 24 hours. SCTr enabled a detailed analysis of adaptive stress response pathways (SRPs), including the unfolded protein response (UPR), oxidative stress response (OSR), heat shock response (HSR), and DNA damage response (DDR). Troglitazone upregulated lipid metabolism genes () along with HSR and UPR activation, with co-expression of , and in subsets of cells. Brefeldin A and tunicamycin strongly induced UPR markers () in subsets of cells, with some also expressing apoptotic () and autophagic () genes, indicating diverse stress responses. Rotenone activated , and in a fraction of cells, accompanied by and mild UPR induction, reflecting heterogeneous mitochondrial stress responses. We scored individual cells using literature-derived SRP gene signatures to characterize overall stress phenotypes and clustered them using a generalized Jaccard metric. The clustering revealed five phenotypic groups spanning cell states associated with homeostasis, adaptive responses, terminal outcomes, autophagy, and apoptosis. By systematically analyzing the distributions of cells in different states across treatments, we visualized dynamic shifts in cellular subpopulations responding to chemicals, revealing early stress responses and potential transitions to cell death. Our findings suggest the utility of SCTr in decoding stress states that could provide possible insights into transitions between cellular adaptive and terminal transitions involved in toxicity. - Source: PubMed
Publication date: 2025/08/26
Shah ImranGallegos DavidRobinette BrianChambers Bryant AEastburn Dennis JBell Douglas ACampbell Michelle RMartos Suzanne NCamiolo SalvatoreWhite Kevin SMartin NicoleMontis GioeleMcComb JoelSeligmann BruceChorley Brian N