EGLN1 Antibody
- Known as:
- EGLN1 Antibody
- Catalog number:
- 32185
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Signalway
- Gene target:
- EGLN1 Antibody
Related genes to: EGLN1 Antibody
- Gene:
- EGLN1 NIH gene
- Name:
- egl-9 family hypoxia inducible factor 1
- Previous symbol:
- C1orf12
- Synonyms:
- SM-20, PHD2, ZMYND6, HIFPH2
- Chromosome:
- 1q42.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-06-16
- Date modifiied:
- 2016-10-05
Related products to: EGLN1 Antibody
Related articles to: EGLN1 Antibody
- PPARγ coactivator 1 alpha (PGC1α) is a master transcriptional coregulator of metabolism, and its activity mirrors many of the effects of hypoxia signaling in prostate cancer (PCa). Whereas PGC1α restrains PCa progression through its association with the estrogen-related receptor alpha (ERRα) and is a predictor of better patient outcome, hypoxia signaling is associated with poor prognosis. However, their interplay in PCa remains poorly understood. Here we show that the PGC1α/ERRα complex reduces the protein levels of Hypoxia Inducible transcription Factor alpha (HIFα). Moreover, loss of PGC1α is associated with the establishment of an autocrine pseudohypoxic state. Mechanistically, the transcriptional complex formed by PGC1α and ERRα binds to the EGLN1 promoter, induces PHD2 expression, and triggers canonical HIFα proteasomal degradation. This mechanism is oxygen-dependent and thus is prevented under severe hypoxia. Importantly, this regulatory axis provides a new component to the tumor-suppressive activity of the PGC1α/ERRα complex. Specifically, EGLN1 silencing partially reverts PGC1α-mediated PCa tumor suppressive properties both in cellulo and in vivo. Our findings are reinforced by a positive correlation between PGC1α/ERRα activity and EGLN1 expression levels in human PCa datasets. Altogether, these results support that PHD2-regulated degradation of HIFα contributes to PGC1α/ERRα-mediated PCa suppression. - Source: PubMed
Publication date: 2026/09/17
Fagoaga-Eugui MaiderMartin-Martin NataliaZabala-Letona AmaiaIriondo OihanaTalamillo AnaValcarcel-Jimenez LoreaPérez-Andrés EncarnaciónCarlivaris OnintzaGarcia-Longarte SaioaMedina-Jover FerranMacchia AliceViñals FrancescTorrano VeronicaCarracedo ArkaitzBerra Edurne - Aneuploidy is pervasive in cancers and contributes to chemoresistance; however, how aneuploidy-inducing stresses, such as infection and hypoxia, promote chemoresistance remains unclear. Here, we identify a prolyl hydroxylase domain protein 1 (PHD1)-E3 ubiquitin ligase TRIM21-cell division cycle protein 20 (CDC20) signaling axis that integrates infection- and PHD1-inhibitory signals to drive aneuploidy and chemoresistance. Analysis of clinical specimens revealed that HPV-positive cervical cancers exhibited reduced CDC20 expression and increased aneuploidy compared with HPV-negative tumors. Through proteomic screening, we found that CDC20 is targeted for degradation by TRIM21, which preferentially recognizes CDC20 when prolines 337 and 340 are non-hydroxylated. Hypoxia and α-ketoglutarate (α-KG) limitation impair the activity of the dioxygenase PHD1, thereby increasing the fraction of non-hydroxylated CDC20. In parallel, infection activates TRIM21. Thus, PHD1 inactivation and infection converge on CDC20 to reduce its abundance, leading to the accumulation of CDC20 substrates, including the separase inhibitor securin and the anti-apoptotic protein MCL1. Infection- and PHD1 inhibition-induced securin accumulation promotes aneuploidy, whereas MCL1 accumulation enhances chemoresistance. In cultured cancer cells and mouse xenograft models, stabilization of CDC20, either through TRIM21 inhibition or PHD1 activation, attenuates aneuploidy and restores chemosensitivity. Together, our study reveals a PHD1-TRIM21-CDC20 signaling axis that integrates hypoxic and infection-associated cues to regulate aneuploidy and chemoresistance, highlighting this pathway as a potential therapeutic target for overcoming chemoresistance. - Source: PubMed
Publication date: 2026/09/04
Zhou Yi-NengXu Fu-JiangYao Cui-FangLi YangHe Yong-SenMa Zhen-ZhenYang Si-YuanTong XiLin YanYuan Yi-YuanZhao Jian-YuanLin Peng-ChengMao Yun-ZiKang YuZhao Shi-MinXu Wei - Glioblastomas are the most common and highly aggressive malignant brain tumors that are difficult to treat. Hypoxia is a significant factor in glioblastoma growth. Previous studies have shown that the inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) significantly suppresses the glioblastoma cell proliferation and modifies the hypoxic regulation. The present study aimed to investigate the impact of hypoxia on the expression of endoplasmic reticulum stress-dependent genes including in U87MG glioblastoma cells in relation to ERN1 inhibition to reveal a possible role of the ERN1 signaling pathway in the hypoxic regulation of these genes' expression. The control U87MG glioblastoma cells (transfected by an empty vector) and ERN1 knockdown cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) were used. Hypoxia was induced at normoxic conditions with dimethyloxalylglycine (0.5 mM for 4 h). RNA was extracted and reverse transcribed. The expression levels of , , , , , and genes were studied by real-time qPCR and normalized to ACTB mRNA. It was established that hypoxia increases the expression level of , , , and in glioblastoma cells with native ERN1. However, the expression levels of two other stress-dependent genes ( and ) were reduced in these glioblastoma cells under hypoxia. Furthermore, inhibition of ERN1 enzymatic activity attenuated the effects of hypoxia on the expression of most of the genes studied in glioblastoma cells, while XIAP gene expression was dramatically increased. The results of this study showed that hypoxia differentially affects the expression of genes related to endoplasmic reticulum stress in glioblastoma cells and is dependent on ERN1 activity. This reflected the ERN1-mediated reprogramming of hypoxic regulation of gene expression. - Source: PubMed
Publication date: 2026/08/31
Halkin Oleh VMinchenko Dmytro OViletska Yuliia MSliusar Myroslava YKhita Olena OFeldman Taia VMinchenko Oleksandr H - The IVS4+919G>A founder variant causes a late-onset, cardiac-predominant form of Fabry disease, yet the severity of cardiac remodeling varies markedly among affected men. We studied 167 unrelated male carriers. Genome-wide association analyses included 81 men aged ≥50 years for left ventricular hypertrophy (LVH; left ventricular mass index [LVMI] ≥ 51 g/m) and septal hypertrophy (interventricular septal thickness at end-diastole [IVSd] ≥ 1.2 cm), and 149 men with plasma globotriaosylsphingosine (lyso-Gb3) measurements. Genotyping was performed with the Axiom Genome-Wide TPM 2.0 Array. Mean LVMI increased from 34.6 ± 11.3 g/m at 20-39 years to 75.1 ± 34.0 g/m at ≥60 years, although substantial variability persisted within each age stratum. rs1435166 and rs2572260, located in the adjacent / region, showed identical associations with LVH (both = 4.14 × 10) and concordant genotypes in all 81 participants (dosage r = 1.00; D' = 1.00), indicating a single regional association signal. The association remained evident in exact testing, Firth logistic regression, and an age-adjusted continuous-LVMI analysis yielded concordant results. In the age-adjusted analysis, each rs1435166 T allele was associated with a 12.8 g/m lower LVMI. Two intergenic variants met the exploratory threshold for septal hypertrophy, whereas no variant reached genome-wide significance for lyso-Gb3. These findings support the hypothesis that inherited genetic background contributes to variation in cardiac remodeling severity among carriers of the same pathogenic GLA variant. Independent replication, regional fine-mapping, and functional validation are required. - Source: PubMed
Publication date: 2026/08/20
Sung Kuo-TzuHsu Chih-YenLu Yung-HsiuHung Chung-LiehNiu Dau-Ming - Studies have shown that fluoride induces cartilage damage, however, the specific mechanism is unknown. In this study, we investigated the effect of fluoride on extracellular matrix metabolism and its molecular regulatory mechanism, using well-established experimental models SW1353 cell line and neonatal rat tibia organ culture. We found that 5 × 10 M fluoride reduced proteoglycan synthesis by 20%, significantly downregulated the expression levels of Aggrecan, Collagen Type II and X Alpha 1 Chain, and upregulated various matrix metalloproteinases. Based on RNA sequencing results, we found that differentially expressed genes were significantly enriched in the hypoxia inducible factor 1 (HIF1) signaling pathway, which ranked second in enrichment significance. Further studies demonstrated that fluoride significantly suppressed the expression of glycolysis-related enzymes, the oxygen consumption rate and glycolytic capacity, leading to notably reduced ATP production. Moreover, fluoride decreased both mRNA and protein level of HIF1α by half through increasing prolyl hydroxylase domain 2 expression by twice. Importantly, stabilizing HIF1α with CoCl effectively reversed the adverse effects of fluoride. Together, these results suggested that fluoride inhibited glycolytic activity by the PHD2/HIF1α signaling pathway, thereby further disrupting the metabolic balance of the cartilage extracellular matrix. - Source: PubMed
Publication date: 2026/08/21
Gui YuMa RuiMa LanZou TinglingZhang KaiqiangGuo Xiaoying