Novel PGK1 determines AR stability dependent on Spk2 and reprograms granular cell glucose metabolism to facilitate ovulation dysfunction
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ABSTRACT:
PROVIDER: PRJNA612177 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11294051_1.fastq.gz | Fastqsanger.gz | |||
| SRR11294051_2.fastq.gz | Fastqsanger.gz | |||
| SRR11294052_1.fastq.gz | Fastqsanger.gz | |||
| SRR11294052_2.fastq.gz | Fastqsanger.gz | |||
| SRR11294053_1.fastq.gz | Fastqsanger.gz |
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Project description:Ovulation disorder is the main characteristic of polycystic ovary syndrome (PCOS), but the concrete molecular mechanism is unclear. Phosphoglycerate kinase 1 (PGK1) plays an important role in the process of glycolytic cycles. Androgen and androgen receptor (AR) are considered as one of the critical factors in the prevalence of hyperandrogenemia and follicular development, and whether PGK1 participates in the metabolic reaction via AR in PCOS remains vague. PGK1 and AR proteins were highly expressed in PCOS luteinized granulosa cells and the PCOS-like mice ovary tissues. PGK1 increased lactate levels and deteriorated PCOS-like mouse metabolic disorder, and importantly, the phenotype of PCOS-like mice was rescued by PTX (paclitaxel) and the PGK1 and AR protein levels also decreased in the ovary. We demonstrated that PGK1 promoted AR translocation into the nuclear, and PGK1 was dependent on the E3 ligase Skp2 to repress the AR ubiquitination to improve the AR stability. In addition, we found that follicular development critical genes MAP2K6, KLF15, LRIG3 and MYOF were regulated by the PGK1-AR axis in the RNA-seq data, and axis also mediated cell proliferation and apoptosis. This study highlights the glycolysis key gene PGK1 to regulate metabolism in granular cell result in etiology of the PCOS. The PGK1-AR axis might provide a new therapy target of PCOS
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Project description:Ferroptosis is restrained by layered antioxidant defenses, yet whether glycolytic enzymes directly constitute ferroptosis-defense machinery remains unclear. Here we identify phosphoglycerate kinase 1 (PGK1) as a non-canonical suppressor of ferroptosis that functions independently of its glycolytic kinase activity. Across pan-cancer bulk and single-cell transcriptomes, glycolysis inversely associates with ferroptosis programs, with PGK1 emerging as a prognostic hub. PGK1 loss in multiple tumor models elicits hallmark ferroptotic features, elevates lipid peroxidation and labile iron, and suppresses xenograft growth, all of which are reversed by liproxstatin-1. Mechanistically, PGK1 physically binds the C-terminal tail of SLC7A11 (aa 471-501) and shields it from ubiquitin-proteasome degradation, thereby sustaining cystine-driven glutathione synthesis and redox homeostasis. This scaffolding role is preserved in a kinase-dead PGK1 mutant, establishing a strict separation between metabolic and ferroptosis-regulatory functions. Restoring SLC7A11 rescues PGK1-deficient tumor growth, whereas a rationally designed competing peptide SLC7A11471-501 (FP-01) disrupts the PGK1-SLC7A11 interface, depletes SLC7A11/GSH, triggers ferroptosis, and suppresses tumor progression in vivo. Collectively, the PGK1-SLC7A11 interaction represents a druggable ferroptosis vulnerability that enables selective ferroptosis induction while sparing essential glycolysis.
2026-07-12 | GSE317428 | GEO
Project description:Comparative gene expression profiling analysis of scRNA-seq data for PGK1 KO and PGK1 WT HCC cells
2026-07-12 | GSE317778 | GEO
Project description:Ferroptosis is restrained by layered antioxidant defenses, yet whether glycolytic enzymes directly constitute ferroptosis-defense machinery remains unclear. Here we identify phosphoglycerate kinase 1 (PGK1) as a non-canonical suppressor of ferroptosis that functions independently of its glycolytic kinase activity. Across pan-cancer bulk and single-cell transcriptomes, glycolysis inversely associates with ferroptosis programs, with PGK1 emerging as a prognostic hub. PGK1 loss in multiple tumor models elicits hallmark ferroptotic features, elevates lipid peroxidation and labile iron, and suppresses xenograft growth, all of which are reversed by liproxstatin-1. Mechanistically, PGK1 physically binds the C-terminal tail of SLC7A11 (aa 471-501) and shields it from ubiquitin-proteasome degradation, thereby sustaining cystine-driven glutathione synthesis and redox homeostasis. This scaffolding role is preserved in a kinase-dead PGK1 mutant, establishing a strict separation between metabolic and ferroptosis-regulatory functions. Restoring SLC7A11 rescues PGK1-deficient tumor growth, whereas a rationally designed competing peptide SLC7A11471-501 (FP-01) disrupts the PGK1-SLC7A11 interface, depletes SLC7A11/GSH, triggers ferroptosis, and suppresses tumor progression in vivo. Collectively, the PGK1-SLC7A11 interaction represents a druggable ferroptosis vulnerability that enables selective ferroptosis induction while sparing essential glycolysis.
2026-07-13 | GSE338472 | GEO
Project description:To identify the site(s) of O-GlcNAcylation on PGK1, we transiently co-expressed Flag-tagged PGK1 and OGT in HEK293T cells. After immunoprecipitation using anti-Flag M2 beads and in-gel trypsin digestion, resulted peptides were subjected to mass spectrometry analysis
2019-11-06 | PXD015659 | Pride
Project description:The present study aimed at studying the rainbow trout egg transcriptome using 9152-cDNA microarrays after natural or controlled ovulation. The analysis of egg transcriptome after natural or controlled ovulation led to the identification of 26 genes. We observed that both hormonal induction and photoperiod control of ovulation induced significant changes in the egg mRNA abundance of specific genes. We demonstrate that hormonal induction of ovulation has an impact on the egg mRNA abundance of specific genes even though the resulting effects on the developmental potential of the egg is so far unknown. In addition, we also identified 1 gene exhibiting a differential mRNA abundance in eggs of varying developmental potential. Analysis of egg transcriptome after natural ovulation (4 samples), photoperiod-controlled ovulation (14 samples), and hormonally-induced ovulation (11 samples).
2010-07-01 | E-GEOD-5928 | biostudies-arrayexpress
Project description:The present study aimed at studying the rainbow trout egg transcriptome using 9152-cDNA microarrays after natural or controlled ovulation. The analysis of egg transcriptome after natural or controlled ovulation led to the identification of 26 genes. We observed that both hormonal induction and photoperiod control of ovulation induced significant changes in the egg mRNA abundance of specific genes. We demonstrate that hormonal induction of ovulation has an impact on the egg mRNA abundance of specific genes even though the resulting effects on the developmental potential of the egg is so far unknown. In addition, we also identified 1 gene exhibiting a differential mRNA abundance in eggs of varying developmental potential. Keywords: Egg quality-dependent
2006-10-03 | GSE5928 | GEO
Project description:We employed an AP-MS approach to map ISG15 modification sites on GAPDH and PGK1 in HEK293T cells by overexpression of FLAG-GAPDH, FLAG-PGK1 or FLAG-GFP together with the ISG15 conjugation enzymes (E1, E2, E3) and wild-type HA-ISG15 or conjugation-defective ISG15-AA. Cells were lysed in physiological buffer, subjected to FLAG-pulldown followed by on-bead digestion and further processing for LC-MS/MS analysis.
2026-03-02 | PXD071724 | Pride
Project description:Running title: More insights into ovulation Purpose:Ovulation is the process by which mature follicles release fertilized oocytes under the stimulation of gonadotropin. This involves the precise interaction and destiny of various cells in the follicle. Granulosa cells (GCs) are the only cells that recognize and respond to ovulation LH (or HCG) signals. Therefore, the classification and deep interpretation of genes in GCs under LH surge stimulation is the key to understand ovulation. Methods: In this study, RNA-seq, Q-PCR, Western blot, gene knockout, gene knockout and other experimental techniques were used to conduct trend and classification analysis of the genes regulated by ovulation signal of LH at the cellular and individual levels. Genes that may be involved in ovulation were screened, identified and were selected for functional verification. Results:(1) Firstly, 7104 and 347 mRNA and Long noncoding RNA (LncRNA) that may be involved in ovulation activity were screened at the gene level by transcriptome sequencing technology, respectively. According to gene expression, they were divided into activated, inhibited and transient activated gene expression patterns. 44 secreted proteins, 62 transcription factors, 22 periodic expression characteristic genes, 10 ovulation process unknown genes, 16 LncRNA-target gene cis pair combinations and 41 highly expressed LncRNA were identified and listed in the three models;(2) The functions of LncRNA Gm12840 and Gm20186 were studied at the cellular level. The results showed that knockdown Gm12840/20186 not only inhibited the proliferation and hormone synthesis of GCs, but also induced cell apoptosis;(3) The function of LncRNA Gm12840 was further studied in mice, and Gm12840 knockout mice were constructed by CRISPR/CAS9 technology: Results It was found that Gm12840 knockout significantly increased the number of antral follicles and ovulation, and significantly inhibited the number of atretic follicles and antral follicles not discharged after ovulation. Gm12840 knockout significantly increased litter size at 2-3 months of age, but also significantly inhibited litter size at 7-9 months of age. Meanwhile, Gm12840 knockout also significantly inhibited the number of follicles growing in the ovary of 11-month-old mice;(4) Finally, transcriptomic sequencing analysis of wilt-type and Gm12840-/- mouse GCs showed 349 genes were differentially expressed. KEGG enrichment analysis and WB results showed that Gm12840 knockout enhanced mTOR and MAPK signals. Conclusions:The above results screened and identified genes with potential research value during ovulation process, and took LncRNA Gm12840 as an example to verify their functions at the cell and individual levels, providing reference for further revealing the ovulation process.
2024-08-27 | GSE182965 | GEO