Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of the peroxisomes was examined in the pathogenic basidiomycete Cryptococcus neoformans. Recent studies reveal the glyoxylate pathway is required for virulence of diverse microbial pathogens of plants and animals. One exception is C. neoformans, in which isocitrate lyase (encoded by ICL1) was previously shown not to be required for virulence, and here this was extended to exclude also a role for malate synthase (encoded by MLS1). The role of peroxisomes, in which the glyoxylate pathway enzymes are localized in many organisms, was examined by mutation of two genes (PEX1 and PEX6) encoding AAA (ATPases associated with various cellular activities)-type proteins required for peroxisome formation. The pex1 and pex6 deletion mutants were unable to localize the fluorescent DsRED-SKL protein to peroxisomal punctate structures, in contrast to wild-type cells. pex1 and pex6 single mutants and a pex1 pex6 double mutant exhibit identical phenotypes, including abolished growth on fatty acids but no growth difference on acetate. Because both icl1 and mls1 mutants are unable to grow on acetate as the sole carbon source, these findings demonstrate that the glyoxylate pathway can function efficiently outside the peroxisome in C. neoformans. The pex1 mutant exhibits wild-type virulence in a murine inhalation model and in an insect host, demonstrating that peroxisomes are not required for virulence under these conditions. An unusual phenotype of the pex1 and pex6 mutants was that they grew poorly with glucose as the carbon source, but nearly wild type with galactose, which suggested impaired hexokinase function and that C. neoformans peroxisomes might function analogously to the glycosomes of the trypanosomid parasites. Deletion of the hexokinase HXK2 gene reduced growth in the presence of glucose and suppressed the growth defect of the pex1 mutant on glucose. The hexokinase 2 protein of C. neoformans contains a predicted peroxisome targeting signal (type 2) motif; however, Hxk2 fused to fluorescent proteins was not localized to peroxisomes. Thus, we hypothesize that glucose or glycolytic metabolites are utilized in the peroxisome by an as yet unidentified enzyme or regulate a pathway required by the fungus in the absence of peroxisomes.
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PMID:Peroxisome function regulates growth on glucose in the basidiomycete fungus Cryptococcus neoformans. 1704 Nov 84

In brain and tumor cells, the hexokinase isoforms, HK-I and HK-II, bind to the voltage-dependent anion channel (VDAC) in the outer mitochondrial membrane. The VDAC domains interacting with these anti-apoptotic proteins were recently defined using site-directed mutagenesis. Now, we demonstrate that synthetic peptides corresponding to the VDAC1 N-terminal region and selected sequences bound specifically, in a concentration- and time-dependent manner, to immobilized HK-I, as revealed by real time surface plasmon resonance technology. The same VDAC1-based peptides also detached HK bound to brain or tumor-derived mitochondria. Moreover, expression of the VDAC1-based peptides in cells overexpressing HK-I or HK-II prevented HK-mediated protection against staurosporine-induced release of cytochrome c and subsequent cell death. One loop-shaped VDAC1-based peptide corresponding to a selected sequence and fused to a cell-penetrating peptide entered the cell and prevented the anti-apoptotic effects of HK-I and HK-II. This peptide detached mitochondrial-bound HK better than did the same peptide in its linear form. Both cell-expressed and exogenously added cell-penetrating peptide detached mitochondrial-bound HK-I-GFP. These results point to HK-I and HK-II as promoting tumor cell survival through binding to VDAC1, thereby inhibiting cytochrome c release and apoptotic cell death. Moreover, VDAC1-based peptides interfering with HK-mediated anti-apoptotic activity may potentiate the efficacy of conventional chemotherapeutic agents.
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PMID:Voltage-dependent anion channel 1-based peptides interact with hexokinase to prevent its anti-apoptotic activity. 1904 77

Sucrose synthase (SUS) is a key enzyme of carbon metabolism in heterotrophic tissues of plants. The Arabidopsis genome contains six SUS genes. Two members of this family, namely AtSUS2 (At5g49190) and AtSUS3 (At4g02280) are strongly and differentially expressed in Arabidopsis seed. Expression analysis was carried out using SUS:promoter-GUS fusion lines in a wild-type genetic background or in a mutant carrying a lesion in the transcription factor LEAFY COTYLEDON 2 (LEC2; At1g28300). The accumulation patterns of mRNA, protein, and SUS activity were altered in the lec2 mutant during seed development 9-18 days after flowering. This indicates that LEC2 acts epistatically on the expression of AtSUS2 and AtSUS3. It appears that LEC2 is required for cotyledon-specific expression of both SUS genes but it is not responsible for expression in the radicle tip during embryo development. The AtSUS2 promoter was induced in planta by feeding of glucose but less so by sucrose and trehalose. Non-phosphorylable glucose analogs such as 3-O-methyl-glucose and 2-deoxyglucose also caused an induction, suggesting that sugar signaling proceeds by a hexokinase-independent pathway, possibly involving hexose sensing. Analysis of transgenic lines carrying of truncated versions of the AtSUS2:promoter fused to Beta-glucuronidase activity revealed an internal 421 bp region that was responsible for expression in seeds. Bioinformatic sequence analysis revealed regulatory cis-elements putatively responsible for the spatio-temporal pattern of AtSUS2 expression such as the SEF3 (aaccca) and W-box (ttgact) motifs. These findings are discussed in relation to the roles played by AtSUS2, AtSUS3 and LEC2 in the biosynthesis of seed storage products in Arabidopsis.
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PMID:Regulation of AtSUS2 and AtSUS3 by glucose and the transcription factor LEC2 in different tissues and at different stages of Arabidopsis seed development. 2222 9


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