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evolution
tunable selectivity may be a general phenomenon among multispecific enzymes involved in posttranslational modification and raises the possibility of variable substrate selectivity among GGTase-I orthologues from different organisms
malfunction
combined FTase/GGTase-I deficiency significantly reduces K-Ras-induced lung tumors and improves survival without obvious pulmonary toxicity
malfunction
combined FTase/GGTase-I deficiency significantly reduces K-Ras-induced lung tumors and improves survival without obvious pulmonary toxicity
malfunction
downregulation or inhibition of GGT decreases synaptogenesis
malfunction
GGTase-I inhibition results in proliferation inhibition associated with G1 arrest and accumulation of cell cycle regulators such as p21CIP1/WAF1
malfunction
high K+ or bicuculline-induced increases in dendritic spine density are significantly abolished by enzyme inhibition. GGTI not only regulates the basal neuronal dendritic growth but also mediates neuronal activity and BDNF-induced dendritogenesis. Dendrite development of Purkinje cells is dramatically impeded by downregulation of GGTIbeta expression or inhibiting GGTI activity in cultured cerebellar slices
malfunction
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loss of enzyme activity results in colonies of round, single-celled organisms that resemble unicellular algae. Enzyme mutants fail to respond to polarized light. Ppggb mutants appear to remain in an undifferentiated state, with no sign of polarity
malfunction
mice with lateral ventricular injection of GGTi-2147, a specific GGTI inhibitor, have significant reduction in the membrane association of Rac1 and in the dendritic spine densities in the hippocampus, the cerebellum, and the frontal cortex
malfunction
overexpression of GGTbeta promotes the linear density of post-synaptic density protein 95 (PSD 95) and synapsin 1, two major molecular markers of synaptogenesis, while downregulation or inhibition of GGT decreases synaptogenesis
malfunction
the related Rac and Ras proteins are not mislocalized in the cdc43DELTA mutant even though they contain similar CaaL motifs, the membrane localization of each of these GTPases is dependent on the prenylation of the CaaX cysteine. The cdc43DELTA mutant has a growth defect at 37°C and 39°C. The cdc43dELTA mutant does not exhibit cell wall defects. The cdc43DELTA mutant is more susceptible to farnesyltransferase inhibitors
malfunction
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overexpression of GGTbeta promotes the linear density of post-synaptic density protein 95 (PSD 95) and synapsin 1, two major molecular markers of synaptogenesis, while downregulation or inhibition of GGT decreases synaptogenesis
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malfunction
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downregulation or inhibition of GGT decreases synaptogenesis
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physiological function
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enzyme GGTase-I is abundantly expressed in human primary glioma tissues. Inhibition or downregulation of GGTase-I markedly decreases the proliferation of glioma cells and induces their apoptosis, while overexpression of GGTase-I promotes cell growth in vitro. Inactivation of GGTase-I eliminates geranylgeranylation of RhoA and Rac1, prevents them from targeting to the plasma membrane, and inhibits Rac1 activity. Overexpressing wild type or constitutively active Rac1 stimulates glioma cell growth, similar to the effect of GGTase-I overexpression. Overexpressing dominant-negative Rac1 or Rac1 with the prenylation site deleted or mutated abrogates GGTase-I-induced proliferation in glioma cells
physiological function
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inhibition or down-regulation using small interference RNA inhibits dendritic development of Purkinje cells. In contrast, up-regulation of enzyme expression promotes dendritic arborization of Purkinje cells. Neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor BDNF promotes membrane association of Rac1 and dendritic development of Purkinje cells in cultured cerebellar slices. The effect of BDNF or high K+ is inhibited by inhibition or down-regulation of enzyme
physiological function
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pharmacological inhibition of protein geranylgeranyltransferase-I induces simultaneous p53-dependent apoptosis and autophagy in airway smooth muscle cells, and autophagy regulates apoptosis induction
physiological function
Cryptococcus neoformans geranylgeranyltransferase-I is involved in high-temperature growth and morphogenesis. The enzyme belongs to the CaaX prenyltransferases (where CaaX indicates a cysteine followed by two aliphatic amino acids and a variable amino acid) that direct the subcellular localization of a large group of proteins by catalyzing the attachment of hydrophobic isoprenoid moieties onto C-terminal CaaX motifs, thus facilitating membrane association. The enzyme-mediated activity is not essential, but is important for thermotolerance, morphogenesis, and virulence. Ggtase-I function is required for full membrane localization of Rho10 and the two Cdc42 paralogues (Cdc42 and Cdc420). Ggtase-I activity are required for full growth in association with macrophages
physiological function
enzyme GGTase-I has a crucial role in the posttranslational modification of Ras proteins. The enzyme is involved in several diseases, e.g. glaucoma via Rho prenylation, and neurological diseases. GGTase-I catalyzes geranylgeranyl isoprenoid linked to the cysteine residue of the CAAX protein through a thioether linkage, which will enhance the hydrophobicity of the CAAX protein. Meanwhile, the formed CAAX-protein-isoprenoid complex is attached to the endoplasmic reticulum surface
physiological function
enzyme GGTase-I has a crucial role in the posttranslational modification of Ras proteins. The enzyme is involved in several diseases, e.g. glaucoma via Rho prenylation, and neurological diseases. GGTase-I catalyzes geranylgeranyl isoprenoid linked to the cysteine residue of the CAAX protein through a thioether linkage, which will enhance the hydrophobicity of the CAAX protein. Meanwhile, the formed CAAX-protein-isoprenoid complex is attached to the endoplasmic reticulum surface
physiological function
importance of GGTase-I in cell proliferation and cell cycle progression
physiological function
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protein geranylgeranyltransferase type I is not required for viability, but is required for cell adhesion, polar cell elongation, and cell differentiation
physiological function
role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. GGTI is localized at the neuromuscular junction and regulates agrin-induced clustering of acetylcholine receptors by interacting with muscle-specific receptor tyrosine kinase. Importance of prenylation in synaptic function. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons
physiological function
role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. Importance of prenylation in synaptic function. GGTI not only regulates the basal neuronal dendritic growth but also mediates neuronal activity and BDNF-induced dendritogenesis. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons
physiological function
role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. Importance of prenylation in synaptic function. GGTI not only regulates the basal neuronal dendritic growth but also mediates neuronal activity and BDNF-induced dendritogenesis. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons. Roles of the enzyme in aging, overview
physiological function
role of geranylgeranyltransferase I-mediated protein prenylation in the brain. GGTI and geranylgeranylation are involved in neurodegenerative diseases, e.g., aging, Alzheimer's disease, multiple sclerosis, and Niemann-Pick disease type C, mechanism of GGTI-mediated isoprenylation in the pathogenesis of neurodegenerative and neurodevelopmental disorders, overview. neuromuscular junction. GGTI is localized at the neuromuscular junction and regulates agrin-induced clustering of acetylcholine receptors by interacting with muscle-specific receptor tyrosine kinase. Importance of prenylation in synaptic function. GGTI promotes neuronal dendritogenesis via increasing the membrane association of Rac1 in CNS neurons
physiological function
the enzyme mediates lipid modification of Rho small GTPases, such as Rho, Rac, and Cdc42, which are important for neuronal synaptogenesis. It promotes the basal and neuronal activity and brain-derived neurotrophic factor (BDNF)-induced dendritic morphogenesis of cultured hippocampal neurons and cerebellar slices. Function and mechanism of geranylgeranyltransferase I in neuronal synaptogenesis, enzyme regulation by factors that promote synaptogenesis, overview. The activities of GGT and Rac are regulated by BDNF
physiological function
deleting beta-subunit CDC43 of geranylgeranyltransferase type I confers hypersensitivity to echinocandins. The membrane localization of Rho is disrupted in the CDC43 mutant, resulting in decreased amounts of glucans in the cell wall, thereby exacerbating the cell wall stress upon caspofungin addition
physiological function
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deletion of CDC43 is lethal in Candida glabrata
physiological function
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the enzyme mediates lipid modification of Rho small GTPases, such as Rho, Rac, and Cdc42, which are important for neuronal synaptogenesis. It promotes the basal and neuronal activity and brain-derived neurotrophic factor (BDNF)-induced dendritic morphogenesis of cultured hippocampal neurons and cerebellar slices. Function and mechanism of geranylgeranyltransferase I in neuronal synaptogenesis, enzyme regulation by factors that promote synaptogenesis, overview. The activities of GGT and Rac are regulated by BDNF
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additional information
FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I
additional information
FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I
additional information
FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I
additional information
FTase and GGTase-I recognize the same CAAX sequence motif in a protein substrate and catalyze the attachment of farnesyl and geranygeranyl groups to the protein, respectively. The X is the key residue that determines the farnesylation or geranylgeranylation of the CAAX-containing protein. When X is serine, methionine or glutamine the protein substrate is preferentially activated by FTase, but when X is leucine or phenylalanine the protein substrate is preferentially activated by GGTase-I
additional information
the enzyme includes two subunits: an alpha subunit (GGTalpha), the catalytic subunit, that is shared with farnesyltransferase, EC 2.5.1.58, and a distinct beta subunit (GGTbeta), which is responsible for substrate binding
additional information
the enzyme includes two subunits: an alpha subunit (GGTalpha), the catalytic subunit, that is shared with farnesyltransferase, EC 2.5.1.58, and a distinct beta subunit (GGTbeta), which is responsible for substrate binding
additional information
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the enzyme includes two subunits: an alpha subunit (GGTalpha), the catalytic subunit, that is shared with farnesyltransferase, EC 2.5.1.58, and a distinct beta subunit (GGTbeta), which is responsible for substrate binding
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