Disease relevance of GBP1

• Two overlapping phage clones contained the entire GBP1 gene [1].
• Importantly, stable expression of a GBP1 transgene in the paclitaxel-sensitive ovarian cancer cell line OVCAR8 was sufficient to confer moderate paclitaxel resistance [2].
• GBP-1 expression was induced by IC, downregulated by angiogenic growth factors, and inversely related to cell proliferation both in vitro in microvascular and macrovascular endothelial cells and in vivo in vessel endothelial cells of Kaposi's sarcoma [3].
• These results define GBP-1 as an important tool for dissection of the complex activity of IC on endothelial cells, and detection and specific modulation of the IC-activated non-proliferating phenotype of endothelial cells in vascular diseases [3].
• Notably, GBP-1 expression was undetectable in the skin, but it was highly induced in vessels of skin diseases with a high-inflammatory component including psoriasis, adverse drug reactions, and Kaposi's sarcoma [4].

Psychiatry related information on GBP1

• Stimulatory (Gs) and inhibitory (G(i)) guanine nucleotide binding protein alpha subunit levels were measured in mononuclear leukocytes from 22 drug-free depressed patients (eight with bipolar disorder, 14 with major depressive disorder) and a comparison group of 17 age- and sex-matched healthy subjects [5].
• In addition to the well-known neurotransmitter systems that are disrupted in mood disorders, critical guanine nucleotide-binding protein (G protein)-coupled signaling pathways are implicated in modulating mood state [6].
• The amyloid precursor protein (APP) of Alzheimer's disease is a transmembrane protein that is cleaved by an uncharacterized enzyme known as alpha-secretase within its extracellular/intraluminal domain after the activation of guanine nucleotide-binding protein-coupled receptors linked to phosphoinositide hydrolysis [7].
• Coupling of D1 dopamine receptors to the guanine nucleotide binding protein Gs is deficient in Huntington's disease [8].
• This is based on nucleotide-dependent self-association of hGBP1, which leads to self-stimulation of its GTPase activity [9].

High impact information on GBP1

• Further studies localized the defect in signal transduction to the interaction between cell-surface receptors and the guanine nucleotide-binding protein [10].
• Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2 [11].
• From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity [11].
• Odorant activation of the enzyme is ligand and tissue specific, and occurs only in the presence of GTP, suggesting the involvement of receptor(s) coupled to a guanine nucleotide binding protein (G-protein) [12].
• These findings strongly support the idea that the coupling factor linking receptor and PPI phosphodiesterase is a guanine nucleotide binding protein analogous to those involved in the activation and inhibition of adenylate cyclase [13].

Chemical compound and disease context of GBP1

• Pertussis toxin pretreatment, which maximally ADP-ribosylated Gi, the guanine nucleotide-binding protein that couples inhibitory receptors to adenylate cyclase and blocks receptor-mediated inhibition of adenylate cyclase, did not interfere with ANF suppression of isoproterenol- or PGE1-elevated cellular cAMP content [14].
• Phosphoinositide hydrolysis in platelets stimulated by thrombin is thought to be regulated by a pertussis toxin-sensitive guanine nucleotide binding protein (G protein) referred to as Gp [15].
• To investigate the possible role of a guanine nucleotide binding protein in transduction of this membrane signal, we examined the effects of pertussis toxin on chemotactic peptide-stimulated inositol phospholipid metabolism in differentiated HL-60 cells labeled with [3H]inositol [16].
• Cells pretreated with pertussis toxin were not responsive to carbachol, indicating the involvement of a guanine nucleotide-binding protein in this inhibitory process [17].
• A radioactive and photoactivatable derivative of NAD+, 2-azido-[adenylate-32P]NAD+, has been synthesized and used with pertussis toxin to ADP-ribosylate Cys347 of the alpha subunit (alpha T) of GT, the retinal guanine nucleotide-binding protein [18].

Biological context of GBP1

• Analysis of endometrial biopsies by Northern blotting and RT-PCR demonstrated that GBP1 mRNA is specifically induced at the midsecretory phase of the menstrual cycle [19].
• We have isolated DNA clones containing the interferon (IFN)-inducible guanylate-binding protein-1-encoding gene (GBP1) from a human genomic library [1].
• The interferon-inducible GBP1 gene: structure and mapping to human chromosome 1 [1].
• The 2880 bp corresponding to the GBP1 cDNA were subdivided into eleven exons which were interrupted by a total of 9500 bp of intron DNA [1].
• GBP1 overexpression is associated with a paclitaxel resistance phenotype [2].

Anatomical context of GBP1

• In situ hybridization analysis revealed that GBP1 mRNA expression is localized in the glandular epithelial cells as well as in the stroma in the immediate vicinity of the glands [19].
• Although the precise function of GBP1 in the receptive human uterus remains unclear, its unique expression overlapping the putative window of implantation suggests that it might serve as a useful marker of uterine receptivity in the human [19].
• The human GBP1 protein, when expressed in transfected COS-1 cells, incorporates radioactivity from the isoprenoid precursor [3H]mevalonate [20].
• Using hybrid rodent cell lines containing human chromosomes, GBP1 was mapped to human chromosome 1 [1].
• The GBP1 gene encodes a large GTPase that is induced by interferon gamma (IFN-gamma) in a variety of eukaryotic cells [2].

Associations of GBP1 with chemical compounds

• Here we present the structure of human GBP1 in complex with the non-hydrolysable GTP analogue GppNHp [21].
• Parallel analysis of the Cancer Cell Line Profiling Array determined that GBP1 expression in a majority of cell lines derived from human tumors of different tissue origin was induced to variable levels following exposure to multiple stress agents including paclitaxel and doxorubicin [2].
• These two mutants had a dominant-negative effect, preventing endogenous wild-type hGBP-1 from efficiently redistributing after aluminum fluoride treatment [22].
• Guanylate-binding proteins (GBPs) were originally described as proteins that are strongly induced by interferons and are capable of binding to agarose-immobilized guanine nucleotides. hGBP1, the first of two members of this protein family in humans, was recently shown to represent a novel type of GTPase that hydrolyzes GTP predominantly to GMP [23].
• A conserved tyrosine kinase-activated signal transduction pathway has recently been identified that comprises the plasma membrane-bound small guanine-nucleotide-binding protein Ras and the protein kinases Raf, MAP-kinase kinase and MAP kinase [24].

Physical interactions of GBP1

• The large GTPase GBP-1 (guanylate-binding protein-1) is a major IFN-gamma (interferon-gamma)-induced protein with potent anti-angiogenic activity in endothelial cells [25].
• Guanine nucleotide-binding protein interacting but unstimulating sequence located in insulin-like growth factor II receptor. Its autoinhibitory characteristics and structural determinants [26].
• SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation Gene-1 [27].
• These results suggest that the native TNF receptor couples to a guanine nucleotide-binding protein to form a large complex structure in human placental membranes [28].
• These data suggest that the pharmacological properties of [125I]L-703606 binding to the human NK1 receptor are similar to those of antagonists of nonpeptide guanine nucleotide-binding protein-coupled receptors and that this ligand will be useful for the biochemical and pharmacological characterization of the human NK1 receptor [29].

Enzymatic interactions of GBP1

• The beta-adrenergic receptor kinase (betaARK) is the prototypical member of the family of cytosolic kinases that phosphorylate guanine nucleotide binding-protein-coupled receptors and thereby trigger uncoupling between receptors and guanine nucleotide binding proteins [30].

Regulatory relationships of GBP1

• The c-Jun amino-terminal kinase (JNK) is activated by various heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, inflammatory cytokines, and stress signals [31].
• One mechanism by which BCR-ABL signals in cells is by activating the small guanine nucleotide binding protein Ras [32].
• Members of the beta isozyme subfamily of the phosphoinositide-specific phospholipases C (PLC beta) have recently been shown to be stimulated by both guanine-nucleotide-binding protein alpha and beta gamma subunits [33].
• Antisera against a guanine nucleotide binding protein from retina cross-react with the beta subunit of the adenylyl cyclase-associated guanine nucleotide binding proteins, Ns and Ni [34].
• Photo-excited rhodopsin activates a guanine nucleotide-binding protein (G-protein) by catalyzing the exchange of bound GDP for GTP [35].

Other interactions of GBP1

• IFN-gamma was, however, a more potent inducer of GBP1 than IFN-alpha [19].
• An ISRE (IFN-alpha-stimulated response element) is necessary and sufficient for the induction of GBP-1 expression by IFN-gamma [25].
• A GTPase-deficient mutant (D184N-GBP-1) operated as a transdominant inhibitor of wild-type GBP-1 and rescued MMP-1 expression in the presence of ICs [36].
• GBP-1 anti-proliferative activity did not affect ERK-1/2 activation, occurred in the absence of apoptosis, was found to be independent of the GTPase activity and isoprenylation of the molecule, but was specifically mediated by the C-terminal helical domain of the protein [3].
• Here we present evidence that hGBP-1 can associate with the Golgi apparatus [22].

Analytical, diagnostic and therapeutic context of GBP1

• The biotinylated three-repeat units of GBP1 were preferentially adsorbed onto gold regions delineated using streptavidin-conjugated quantum dots (SAQDs) [37].
• Redistribution from the cytosol to the Golgi was observed by immunofluorescence and subcellular fractionation after aluminum fluoride treatment, suggesting that it occurs when hGBP-1 is in its GTP-bound state [22].
• Characterization by two-dimensional peptide mapping of the gamma subunits of Ns and Ni, the regulatory proteins of adenylyl cyclase, and of transducin, the guanine nucleotide-binding protein of rod outer segments of the eye [38].
• Fluorimetry and isothermal titration calorimetry were applied to prove that only one nucleotide binding site is present in hGBP1 [39].
• In thyroid cells, the alpha-subunit of the stimulatory guanine nucleotide binding protein (Gs alpha) acts as signal transducer between the TSH receptor and the adenylate cyclase (AC), and it regulates both growth and function [40].

References