Disease relevance of GLB1

• GM1-gangliosidosis is a lysosomal storage disease caused by a deficiency of acid beta-galactosidase [1].
• Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B [2].
• The data demonstrate that the mobile group II intron from Lactococcus lactis can be targeted to insert into and repair mutant lacZ (approved gene symbol GLB1) and beta-globin (approved gene symbol HBB) genes with high efficiency and fidelity in model systems in bacteria [3].
• When maize Type I regenerable callus was exposed for 24 h to 0.1 m M ABA or a water stress induced by 0.53 M mannitol, GLB1 was produced as determined by Western analysis [4].
• Morquio-B disease, spondyloepiphyseal dysplasia associated with acid beta-galactosidase deficiency. Report of three cases in one family [5].

Psychiatry related information on GLB1

• This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon [6].
• The Minnesota Multiphasic Personality Inventory 2 (MMPI-2) was administered to 19 LNP subjects self-described as markedly lactose intolerant (S-LNP), 13 LNP subjects who denied lactose intolerance (A-LNP), and 10 lactase-persistent individuals who believed they were lactose intolerant (S-LP) [7].
• The adjustments for age, height, weight, smoking, alcohol consumption, and physical exercise in the multiple regression analysis did not reveal any significant relationships between the lactase genotypes and BMDs at lumbar (P = 0.16), femoral neck (P = 0.99) or total hip (P = 0.96) sites [8].
• Twelve parents of children with genetic diseases (Klinefelter syndrome, trisomy 21, lactase deficiency, phenylketonemia, Noonan syndrome, ichthyosis, Prader-Willi syndrome, and trisomy 13) were tested with the Tennessee Self-Concept Scale prior to and immediately after genetic counseling [9].

High impact information on GLB1

• Identification of these molecules has yielded clues to the biochemical pathways that ultimately result in transcriptional activation via PPAR-gamma and C/EBP [10].
• Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiation [10].
• We conducted a genotype-phenotype association study in 470 Tanzanians, Kenyans and Sudanese and identified three SNPs (G/C-14010, T/G-13915 and C/G-13907) that are associated with lactase persistence and that have derived alleles that significantly enhance transcription from the LCT promoter in vitro [11].
• The switch from short- to long-term facilitation induced by behavioral sensitization in Aplysia involves CREB-like proteins, as well as the immediate-early gene ApC/EBP [12].
• Using the bZIP domain of ApC/EBP in a two-hybrid system, we have cloned ApCREB2, a transcription factor constitutively expressed in sensory neurons that resembles human CREB2 and mouse ATF4 [12].

Chemical compound and disease context of GLB1

• Subjects were considered deficient in lactase if breath-hydrogen excretion exceeded 0.20 ml per min above fasting at 2 hr after a lactose load of 2 g per kg of body weight (maximum 50 g) [13].
• We determined the prevalence of lactase deficiency by analysis of respiratory hydrogen (H2) in 30 women with idiopathic postmenopausal osteoporosis and in 31 female control subjects without evidence of metabolic bone disease [14].
• Taken together, these results demonstrate that the steroid-induced expression of C/EBP alpha is necessary to mediate the glucocorticoid G1 cell cycle arrest of rat hepatoma cells and implicates a role for this transcription factor in the growth control of liver-derived epithelial tumor cells [15].
• Alpha-1 acid glycoprotein/enhancer-binding protein (AGP/EBP) (C/EBPbeta), a member of the C/EBP family, is one of the key transcription factors responsible for the induction of a wide array of genes, some of which are expressed during the acute-phase response [16].
• Impaired elastogenesis in Hurler disease: dermatan sulfate accumulation linked to deficiency in elastin-binding protein and elastic fiber assembly [17].

Biological context of GLB1

• Transfection with a vector carrying the R201C mutation gave rise to a residual GLB1 activity, which, interestingly, was severely reduced in transfection with the L436F/R201C allele [18].
• Some common amino acid substitutions [c.1445G>A (p.Arg482H), c.622C>T (p.Arg208His), c.175C>T (p.Arg59Cys) and c.176G>A (p.Arg59His)] were present in the GLB1 enzyme of several patients, all of Mediterranean origin, suggesting a common origin [19].
• In this report we provide evidence that a 67-kD catalytically inactive form of beta-galactosidase produced by alternative splicing demonstrates immunological and functional similarity and sequence homology to the 67-kD EBP, suggesting that the two might be the same [20].
• We and others have previously shown that a 67-kD cell surface elastin/laminin-binding protein (EBP) is responsible for cell adhesion to elastin and laminin and for mediating the process of elastin fiber assembly, but the nature of this protein was unknown [20].
• Three adult patients with acid beta-galactosidase deficiency/GM1 gangliosidosis who were from two unrelated families of Scandinavian descent were found to share a common point mutation in the coding region of the corresponding gene [21].

Anatomical context of GLB1

• Since the GLB1 activity of the patient's leukocytes was very low and compatible with both the type-I and the type-II form of the disease, the potential impact of each mutation was investigated by expression studies in COS1 cells, and Western blots [18].
• The purpose of this study is to determine effects of GLB1, PPCA and NEU1 gene mutations on elastogenesis in skin fibroblasts [22].
• We conclude that the presence of genetic lesions in both GLB1 and EBP coding region does not directly predict impaired elastogenesis and that elastic fiber assembly has to be evaluated specifically in each case [19].
• The present study provides a novel and natural model validating functional roles of S-Gal in elastogenesis and elucidates an association between impaired elastogenesis and the development of connective-tissue disorders in patients with Morquio B disease and in patients with an infantile form of GM1-gangliosidosis [23].
• The cDNA was also transfected into COS-1 cells and into the EBP-deficient smooth muscle cells (SMC) from sheep ductus arteriosus (DA) [24].

Associations of GLB1 with chemical compounds

• In addition, sequence homology among this splice variant of human beta-galactosidase, sheep EBP, and NH2-terminal sequences of some elastases suggests that these proteins share a common ligand-binding motif that has not been previously recognized [20].
• Amlodipine-induced p21(Waf1/Cip1) promoter activity and expression were abrogated by C/EBP-alpha antisense oligonucleotide or by the GR antagonist RU486 [25].
• These experiments reveal that, in ferric SOLly GLB1, one of the histidine planes is rotated 20 degrees (+/-10 degrees ) away from a N(heme)-Fe-N(heme) axis [26].
• When both Type I and Type II regenerable cultured tissues were exposed to regeneration medium without ABA or mannitol, several GLB1 antibody immunoreactive proteins were produced [4].
• Metabolic pulse labeling of the 67-kD EBP with radioactive serine and further chase of this tracer indicated that both normal fibroblasts and fibroblasts from patients with Costello syndrome initially synthesized comparable amounts of this protein; however, the fibroblasts from Costello syndrome patients quickly lost it into the conditioned media [27].

Physical interactions of GLB1

• New mutations in the PPBG gene lead to loss of PPCA protein which affects the level of the beta-galactosidase/neuraminidase complex and the EBP-receptor [28].
• RB formed stable complexes with all three C/EBP family members [29].
• The identical effect was achieved after stimulation with a VGVAPG synthetic peptide, reflecting the elastin-derived domain known to bind to the 67-kDa elastin-binding protein [30].
• Our previous studies have established that a cell-surface 25-kDa elastin-binding protein of Staphylococcus aureus (EbpS) mediates binding of this pathogen to the extracellular matrix protein elastin [31].

Regulatory relationships of GLB1

• These studies raise the possibility of interactions between individual members of the C/EBP and activating transcription factor/cyclic-AMP response element binding protein families potentially contribute to the tight transcriptional control rendered by the CFTR gene promoter [32].
• C/EBP alpha mutants incapable of inhibiting CDK2 activity in vitro do not inhibit proliferation in cultured cells [33].
• Upregulation of MMP-2 activation by ED led to enhanced melanoma cells invasion through S-Gal occupancy [34].
• A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus sequence upregulates matrix metalloproteinase-1: biochemical and computational analysis [35].

Other interactions of GLB1

• The reduction in GLB1 and EBP confirms that PPCA is essential for their integrity [28].
• This protein forms a high-molecular-weight complex with the hydrolases beta-galactosidase (GLB1) and neuraminidase (NEU1) [28].
• Also, the detection of specific activating transcription factor/cyclic-AMP response element binding protein antigens by antibody supershift analysis of nuclear complexes suggest that species of this family of transcription factors could be involved in the formation of complexes with C/EBP delta within the CFTR gene inverted CCAAT-like element [32].
• We show that C/EBP alpha can cooperate with p21 to inhibit CDK2 activity in vitro [33].
• Furthermore, we demonstrated that the complexes containing RB and C/EBP proteins directly interacted with C-EBP binding site on DNA [29].

Analytical, diagnostic and therapeutic context of GLB1

• Elastic fiber formation and the EBP mRNA expression were examined by immunofluorescence with an anti-tropoelastin antibody and RT-PCR selective for EBP in skin fibroblasts with these lysosomal enzyme deficiencies [22].
• Northern blot analysis showed the acid beta-galactosidase message to be of normal size and quantity in two juvenile and four infantile cases and of normal size but reduced quantity in two infantile cases [36].
• To test this, we used electrophoretic mobility shift assays to demonstrate that the majority of the binding to the inverted CCAAT element, between -135 and -116, was easily competed for by binding to cognate nucleotide sequences for CCAAT-enhancer binding protein (C/EBP) [32].
• We studied 103 CF infants born in north-east Italy, diagnosed following neonatal screening: assay of immunoreactive trypsin (IRT) from a heel-prick blood sample followed by a measurement of meconium lactase in cases with raised IRT [37].
• 4. Similarly, c/EBP transcripts were only detected in treated cell cultures, but MRP1, its isoforms 3-5 as well as MDR-1 were increased threefold after dosing with Aroclor 1254 [38].

References