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Gene-based analysis of the 342 genes in the replication sample using SKAT-O identified one gene, GLS2, significantly associated with complicated Staphylococcus aureus bacteremia(p = 1.2 x 10-4) after Bonferroni correction. The strongest association across all 10,931 variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10-4). This variant is strongly correlated with a missense variant (rs2657879)
This study assessed the relation of GLS2 downregulation in glioblastoma cells to its methylation and TP53 status. Aberrant methylation of CpG islands, appear to contribute to silencing of GLS2 in glioblastoma cells by a mechanism bypassing TP53 mutations.
Non-glutaminolysis function of GLS2 inhibits migration and invasion of hepatocellular carcinoma cells by repressing the epithelial-mesenchymal transition via the Dicer-miR-34a-Snail axis.
observe that while miR-23 is capable of down-regulating the shortened KGA 3'UTR, it has only minor impact on the full-length KGA 3'UTR, demonstrating that additional potent negative regulation of GLS expression exists beyond this single microRNA targeting site
the crystal structure of full-length KGA and present a small-angle X-ray scattering model for full-length GLS2. These structures explain these proteins' compromised ability to assemble into catalytically active supra-tetrameric filaments, as previously shown for GAC.
Cox multivariate regression analysis demonstrated that DUOX1, GLS2, FBP1 and age were independent risk factors for the prognosis of HCC patients after surgery
As a p53 target, GLS2 mediates p53's function in metastasis suppression through inhibiting Rac1.
IDO, through GCN2 kinase activation, downregulates the levels of TCRcomplex tchain and cMyc, resulting in the suppression of Tcell proliferation and a reduction in the levels of LDHA and GLS2
GABAergic neurons and astrocytes express Gls and Gls2 isoenzymes in nucleus and mitochondria, in addition to glutamatergic neurons
Phosphate-activated glutaminase and GAD65/67 concentrations are compared in Alzheimer's disease cerebellum versus normal cerebellum controls
GLS2 expression is significantly decreased in hepatocellular carcinoma.
Silencing GLS or overexpressing GLS2 induces growth inhibition in glioma cell lines.
GLS2 is acting, at least in part, downstream of p73 in neuronal differentiation and highlight a possible role of p73 in regulating neurotransmitter synthesis.
combination of negative modulation of glutaminase isoforms arising from GLS gene with the introduction of the GLS2 gene product, GAB, may in the future provide a useful means to curb glioblastoma growth in situ
Epigenetic silencing of Gls2 via promoter hypermethylation is common in human liver and colon cancers.
The present study was to investigate the potent effect of GLS2 on radioresistance of cervical carcinoma.
GLS2 is a bona fide TAp63 target gene.
LGA circumvents, by an as yet unknown route, the most common mechanism of O6-methylguanine-DNA methyltransferase (MGMT) gene silencing.
Study demonstrated expression of alternative transcripts of the mammalian Gls2 gene. Transcriptional mechanisms giving rise to GLS2 variants and isolation of novel GLS2 transcripts in human, rat and mouse are presented.
GLS2 is resistant to BPTES; GLS1 mutants created reflecting differences between GLS2 and GLS1 sequence in region of BPTES binding; mutant proteins lost inhibition by BPTES; amino acid sequence alignment GLS2 versus GLS1
Data (including data from studies in knockout/transgenic mice) suggest Ppp2ca supports cortical neuronal growth and cognitive function via regulating p73/Gls2 signal transduction in neurons of hippocampus. Ppp2ca gene knock-out results in embryonic cortical atrophy with learning/memory deficits. (Ppp2ca = protein phosphatase 2a catalytic subunit alpha isoform; p73 = transformation related protein 73; Gls2 = glutaminase-2)
Gls2 expression is regulated by the dietary protein/carbohydrate ratio. This effect was not observed in Ppara-null mice.
Phosphate-activated glutaminase (GLS2) is a p53-inducible regulator of glutamine metabolism and reactive oxygen species
The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. This protein is functionally similar to the kidney glutaminase but is a little smaller in size. Originally thought to be liver-specific, this protein has been found in other tissues as well. At least one transcribed pseudogene has been found for this gene.
, L-glutamine amidohydrolase
, breast cell glutaminase
, glutaminase I
, glutaminase liver isoform, mitochondrial
, phosphate-activated glutaminase
, phosphate-dependent glutaminase
, liver mitochondrial glutaminase