Ask about this productRelated genes to: INSIG1 antibody
- Gene:
- INSIG1 NIH gene
- Name:
- insulin induced gene 1
- Previous symbol:
- -
- Synonyms:
- CL-6, MGC1405
- Chromosome:
- 7q36.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-05-15
- Date modifiied:
- 2016-10-05
Related products to: INSIG1 antibody
Related articles to: INSIG1 antibody
- Stable lentiviral vector producer cell lines represent a promising platform for scalable and cost-efficient vector manufacturing, yet their productivity is often limited by intrinsic host-cell constraints. In this study, we aimed to identify cellular factors restricting LVV production in stable doxycycline-inducible GPRTG producer cell lines and to evaluate whether targeted host-cell engineering can improve vector yield. Comparative transcriptomic analysis of high- and low-producing clones revealed distinct differences in cellular pathways related to transcription, translation, energy metabolism, lipid homeostasis, stress response, and chromatin regulation. Based on differential gene expression, candidate genes were modified by CRISPR/Cas9-mediated knockout or overexpression and functionally analyzed in a low-producing clone. Single-gene KO screening identified H1-2, ADAMTS1, INSIG1, GADD45B, and HSPA1B to increase cell-specific LVV productivity up to 2.6-fold, with H1-2 showing the strongest effect. In addition, combinatorial disruption further improved productivity. In contrast, overexpression of selected candidates did not enhance LVV production. Overall, our results demonstrate that transcriptomics-guided host-cell engineering is an effective strategy to identify and relieve intrinsic bottlenecks in stable LVV producer cell lines. - Source: PubMed
Publication date: 2026/07/21
Röscheise JonaEberle Lena-MarieLaux HolgerOtte Kerstin - The fertility of boars is affected by testicular development and spermatogenesis, Sertoli cells (SCs) play a central role in these processes and are regulated by multiple genes and factors. Insulin-induced gene 1 (INSIG1) is a transmembrane protein involved in various physiological processes, such as cell proliferation, differentiation, and cholesterol metabolism. However, the role of INSIG1 in SCs and development of porcine testes has not been reported. In this study, we reported that the expression level of INSIG1 gradually increased in testicular tissues at 2, 80, and 240 days. In vitro, transfection of SCs with the overexpression plasmid pBI-INSIG1 and interference fragment siRNA indicated that INSIG1 could cause cell cycle arrest and inhibit cholesterol production and cell proliferation. Western blotting and immunofluorescence staining revealed that INSIG1 deactivated the Wnt/β-catenin signaling pathway by downregulating the expression of WNT1 and reducing the translocation of β-catenin to the nucleus. Activation of the Wnt/β-catenin signaling pathway mitigates INSIG1-mediated effects, including the inhibition of SCs proliferation and the upregulation of androgen receptor (AR) levels. Our results indicated that INSIG1 plays a significant role in the proliferation and maturation of porcine SCs, revealing emerging directions to investigate in both reproductive biology and agricultural sciences. - Source: PubMed
Publication date: 2026/07/16
Zhang ShaoxuanZhou HangLiu SiminLi JingWang DaliSun BoxingSun HaoLiang Shuang - Cholesterol overload contributes to metabolic dysfunction-associated steatohepatitis (MASH) progression. One major pathway that limits hepatic cholesterol accumulation is export via VLDL secretion. While sterol regulatory element-binding protein (SREBP) activity is suppressed by insulin-induced gene 1 (INSIG1) under high sterol conditions, VLDL secretion nonetheless persists to prevent lipotoxicity and liver injury, presenting an unresolved paradox in cholesterol sensing and lipoprotein export. Here, we identified a cholesterol-responsive interaction between nuclear factor erythroid 2 related factor-1 (NFE2L1) and INSIG1 that preserved cholesterol homeostasis by sustaining VLDL secretion. Liver-specific NFE2L1 deletion elevated INSIG1 abundance, suppressed SREBP1 activation, and impaired VLDL secretion, leading to hepatic cholesterol accumulation and liver injury. Mechanistically, NFE2L1 bound to INSIG1 via its N-terminal homology box 2 (NHB2) domain; free cholesterol strengthened this interaction to promote INSIG1 degradation, thereby enabling SREBP1 activation and VLDL export. In NFE2L1-deficient mice, WT NFE2L1, but not a mutant NFE2L1 form unable to interact with INSIG1 (NHB2-deleted mutant, ΔNHB2), restored SREBP1 activity and VLDL secretion. Lipidomics analysis revealed that NFE2L1 deficiency reduced serum triglyceride composition, which was restored exclusively by WT NFE2L1. In a murine MASH model, NFE2L1 overexpression activated SREBP1/2, lowered hepatic cholesterol, and attenuated liver injury, inflammation, and fibrosis, without elevating atherogenic lipoproteins owing to compensatory LDL receptor upregulation. Together, these findings explain how VLDL secretion capacity was maintained under cholesterol excess and identify the NFE2L1/INSIG1 axis as a sterol-responsive safeguard for hepatic lipid homeostasis and a potential therapeutic target for MASH. - Source: PubMed
Publication date: 2026/07/15
Deng ShijunFreed Jessica ELee Grace YAskin GizelCao ZheCakici ÖzgürYuan BoHui Sheng TonyInouye Karen EGraupera IsabelHotamışlıgil Gökhan S - Metabolic dysfunction-associated steatohepatitis (MASH) affects 1.5%-6.5% of the global population, yet its mechanisms remain incompletely understood. Cholesterol overload is a key driver of MASH, suggesting that targeting cholesterol sensing may offer therapeutic benefits. In this issue, Deng et al. identified nuclear factor erythroid 2-related factor 1 (NFE2L1) as a critical regulator linking cholesterol sensing to VLDL-mediated lipid export. Mechanistically, NFE2L1 interacts with insulin-induced gene 1 (INSIG1) and promotes its degradation in hepatocytes. This cholesterol-dependent NFE2L1-INSIG1 interaction sustains SREBP activation and VLDL secretion to maintain hepatic and systemic lipid homeostasis. Moreover, the study by Deng et al. indicates that hepatic NFE2L1 overexpression decreases INSIG1 abundance and ameliorates MASH progression, highlighting its therapeutic potential. - Source: PubMed
Publication date: 2026/07/15
Zang MengweiLi Yu - Dysregulated cholesterol metabolism has been implicated in several aging-associated disorders, including osteoarthritis (OA). 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the key enzyme in cholesterol biosynthesis, but the role of HMGCR in OA and the underlying mechanism remain unclear. In this study, we found that HMGCR fibroblasts (FLSs) were significantly increased in the knee synovium of OA patients and OA mice. Elevated expression of HMGCR in synovial FLSs was positively correlated with cellular senescence and OA progression. The inhibition of HMGCR reversed cellular senescence of FLSs induced by TNF-α in vitro. Additionally, the HMGCR-mediated cholesterol biosynthetic pathway contributed to cellular senescence. Targeted inhibition of HMGCR in synovial FLSs via intra-articular adeno-associated virus delivery effectively reversed cellular senescence of FLSs and mitigated synovitis, cartilage degradation, and pain behaviors in OA mice. Mechanistically, the phosphorylation of AKT1 at Ser473 enhanced its binding to Lys140 of Insig1, facilitating AKT1-Insig1 complex formation. The activation of AKT1 induced the phosphorylation of Insig1 at Ser189 and the dissociation of Insig1 from sterol regulatory element‑binding protein cleavage‑activating protein (SCAP), which contributed to HMGCR transcription and cellular senescence of FLSs. Collectively, our study reveals a novel mechanism of HMGCR-driven cellular senescence of FLSs in OA, which highlights HMGCR as a promising therapeutic target for OA. - Source: PubMed
Publication date: 2026/07/13
Zhang XiaoqiZhou SiruLiu XiXiang WeiPeng XiuqinTian YuLi SongWang HailinLiao BoFang ShunzhengJin RunzeWu JinhuiBai ChuanqingZhang WeiHuang BoLi BingfeiChen LifengChen LinZhang BinNi Zhenhong