Similar Datasets
Project description:We identified several hub genes and key pathways associated with GAC initiation and progression by analysising the microarray data on DEGs, whcih provided a detailed molecular mechanism underlying GAC occurrence and progression.
2019-06-10 | GSE118916 | GEO
Project description:Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 at lysine 22 (rpL40K22me3) by the lysine methyltransferase (KMT) SMYD5 regulates mRNA translation output to promote gastric adenocarcinoma (GAC) malignant progression with lethal peritoneal ascites. A biochemical-proteomic strategy identifies the mono-ubiquitin fusion protein partner rpL40 as the principal physiologic substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprograms protein synthesis to attenuate oncogenic gene expression signatures. SMYD5 and rpL40K22me3 are upregulated in GAC patient samples and negatively correlate with clinical outcomes. SMYD5 ablation in vivo in familial and sporadic mouse models of malignant GAC blocks metastatic disease including peritoneal carcinomatosis (PC). Suppressing SMYD5 methylation of rpL40 inhibits human cancer cell and patient-derived GAC xenograft growth and renders them hypersensitive to PI3K/mTOR inhibitors. Finally, combining SMYD5 depletion with PI3K/mTOR inhibition and CAR-T administration cures an otherwise lethal in vivo mouse model of aggressive GAC-derived PC. Together, our work uncovers a ribosome-based epigenetic mechanism that facilitates evolution of malignant GAC and nominates SMYD5 targeting as part of a potential cornerstone combination therapy to treat a deadly cancer.
2024-03-01 | GSE238257 | GEO
Project description:The gene GLS generates the phosphate activated glutaminase C (GAC) isoform by alternative splicing. GAC, compared to the other isoform, kidney-type glutaminase (KGA), has been characterized as more active and particularly important for cancer cell growth. Very little is known about post-translational modifications regulating GAC function. Hereby we describe the identification of a phosphorylation on the serine 95, located at the GLS N-terminus, a domain shared by both isoforms. A GAC phosphomimetic mutant (S95D) ectopically expressed in breast cancer cells presented decreased enzymatic activity, and its expression impacted on cell’s glutamine uptake, glutamate release and intracellular glutamate levels (compared to expressing wild type GAC) without changing GAC sub-cellular localization. Curiously, replacing S95 by an alanine in the ectopically expressed GAC (S95A) increased cell proliferation and migration. Taken together, these results reveal that GAC is post-translationally regulated by phosphorylation, which impacts on cancer phenotype.
2018-08-13 | PXD008338 | Pride
Project description:The phylum of Apicomplexa groups intracellular parasites that employ substrate-dependent gliding motility to invade host cells, egress from the infected cells and cross biological barriers. The glideosome associated connector (GAC) is a conserved protein essential to this process. GAC facilitates the association of actin filaments with surface transmembrane adhesins and the efficient transmission of the force generated by myosin translocation of actin to the cell surface substrate. Here, we present the crystal structure of Toxoplasma gondii GAC and reveal a unique, supercoiled armadillo repeat region that adopts a closed ring conformation. Characterisation of the membrane binding interface within the C-terminal PH domain as well as an N-terminal fragment necessary for association with F-actin suggest that GAC adopts multiple conformations. A multi-conformational model for assembly of GAC within the glideosome is proposed
2023-05-10 | PXD039335 | Pride
Project description:Chip-seq experiment used to identify the binding sites of alternative σ factor σE in Streptomyces coelicolor. We access the binding sites with and without EtOH stress condition (see methods). To capture the binding of σE, the σE gene was tagged on genome by HA (Human Influenza hemagglutinin derived) epitope (TAC CCA TAC GAC GTC CCA GAC TAC GCT) on its C-terminus, wild type strain without tagged σE served as negative control.
2023-11-29 | E-MTAB-10987 | biostudies-arrayexpress
Project description:We identified SMYD5 (SET and MYND Domain-Containing Protein 5) physiologically methylates core ribosomal protein L40 at lysine 22 (rpL40K22me3).In mouse GAC model, we observed rpL40K22me3 stoichiometry is saturating in both normal and GAC tissue.
2024-06-04 | PXD052359 | Pride