Disease relevance of PRB3

• PRB3 null mutations result in absence of the proline-rich glycoprotein Gl and abolish Fusobacterium nucleatum interactions with saliva in vitro [1].
• We demonstrate that the activation of a G1 cyclin, cyclin D2, is an early event following infection with EBV and that cyclin D2 activation is dependent on the expression of viral genes [2].
• Recent data suggest that cyclin-dependent kinases (Cdks) regulated by G1 cyclins (D type and E) are responsible for the primary phosphorylation of the retinoblastoma protein prior to the G1/S boundary [3].
• We identified two different exonic point mutations causing beta-glucuronidase (beta G1) deficiency in two Japanese patients with mucopolysaccharidosis type VII (MPSVII) [4].
• For immunoscintigraphic localization of human breast cancer two monoclonal antibodies (mabs) 12H12 (immunoglobulin G1) and BM-2 (immunoglobulin G3) were developed [5].

High impact information on PRB3

• Previous results have demonstrated that AT cells are defective in the G1/S checkpoint activated after radiation damage and that this defect is attributable to a defective p53 signal transduction pathway [6].
• Saccharomyces cerevisiae cells treated with rapamycin irreversibly arrested in the G1 phase of the cell cycle [7].
• The resulting lymphoblastoid cell line has secreted immunoglobulin G1 of the kappa type continuously for 2 years [8].
• Increased cytokine secretion was specifically inhibited by G1, an anti-P-selectin mAb that prevents P-selectin from binding to its ligand (P-selectin glycoprotein ligand-1) on myeloid cells [9].
• Thus, the progression of resting B lymphocytes into the G1 phase of the cell cycle can be reconstituted in the absence of virus by the cooperation of two of the six viral genes required for immortalization [2].

Chemical compound and disease context of PRB3

• Relative to the G1 glycoprotein of other HPS-associated hantaviruses, an additional potential glycosylation site was found but this is located in the predicted cytoplasmic domain and is therefore unlikely to be glycosylated [10].
• C6 glioma cultured continuously in the presence of 1 mM valproate exhibited a significant depression of exponential growth but attained confluency one day later, when the majority of cells entered the G1 phase of the cycle [11].
• Bufalin induces apoptosis and the G0/G1 cell cycle arrest of endometriotic stromal cells: a promising agent for the treatment of endometriosis [12].
• Valproic acid suppresses G1 phase-dependent sialylation of a 65kDa glycoprotein in the C6 glioma cell cycle [11].
• Among these compounds, mimosine, a plant-derived amino acid has shown an antineoplastic effect on human lung or pancreatic cancer xenografts in addition to cell cycle arrest in the late G1 phase [13].

Biological context of PRB3

• The amino terminus contained repeating sequences of Ser-Gln-Gly-Pro-Pro-Pro-Arg-Pro-Gly-Lys-Pro-Glu-Gly-Pro-Pro-Pro- Gln-Gly that had significant compositional and sequence homology to that encoded by exon 3 of the PRB3 gene [14].
• This C nucleotide insertion leads to a frameshift with a premature termination codon that probably results in markedly reduced or absent PRB3 gene expression [1].
• The four exons, including splice junctions, for both PRB3 alleles of this subject were completely sequenced [1].
• The amino acid sequence G(1)-P(2)-P(3)-P(4)-H(5)-P(6)-G(7)-K(8)-P(9) occurs twice in the proline-rich glycoprotein (PRG) found in human parotid saliva [15].
• Each of these two amino acid changes reduced the beta G1 activity of the corresponding mutant beta G1 expressed following transfection of COS cells with expression vectors harboring the mutated cDNAs [4].

Anatomical context of PRB3

• Together, these results suggest that this subject does not express the PRB3 gene and that one of the consequences is an altered ability to interact with a bacterium known to colonize the oral cavity [1].
• Mechanisms for this chemoprevention are previously linked to all-trans retinoic acid (RA) signaling growth inhibition at G1 in carcinogen-exposed immortalized human bronchial epithelial cells [16].
• Mutated cDNA clones, including the entire coding sequence, were isolated using the polymerase chain reaction (PCR) products derived from beta G1-deficient fibroblasts [4].
• In contrast, expression in proliferating embryonic peripheral nervous system cells occurs during interphase as a brief pulse that initiates before and overlaps with S phase, demonstrating the presence of a G1 phase in these embryonic neural cell cycles [17].
• G1, G2, and G4 co-immunoprecipitated with G5, and G4 co-immunoprecipitated with G8, but the putative dimers were retained in the endoplasmic reticulum (ER) [18].

Associations of PRB3 with chemical compounds

• Alleles at the PRB3 locus coding for a disulfide-bonded human salivary proline-rich glycoprotein (Gl 8) and a null in an Ashkenazi Jew [19].
• (formula; see text) To understand the structural basis of F. nucleatum binding, we screened glycolipids and neoglycolipids carrying carbohydrate structures related to those of the PRG for receptor activity; components with unsubstituted terminal lactosamine residues best supported adherence [14].
• Amino acid analysis of the protein core showed predominantly proline, glycine, and glutamic acid/glutamine, a characteristic of proline-rich glycoproteins (PRG) [14].
• Since proline is the major amino acid present in native PRG, these localized conformations may contribute to PRG's global conformation and act as a primary force in determining its biological activities [20].
• Exchange lifetime data and previously reported hydrogen----deuterium exchange experiments suggest that the PRG histidine N tau H protons are not involved in hydrogen-bonds [21].

Analytical, diagnostic and therapeutic context of PRB3

• The solution-state conformations of eight proline-containing peptide fragments found in human salivary proline-rich glycoprotein (PRG) were investigated in 2 x distilled water (treated with metal ion chelating resin) using 13C-nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy [20].
• The beta G1-specific mRNA levels were normal, as determined by northern blot analysis [4].
• For the assay of D-methotrexate impurity in commercial methotrexate, L-methotrexate was hydrolyzed with carboxypeptidase G1, and the remaining D-methotrexate was quantitated by high-performance liquid chromatography [22].
• Using a two-hybrid assay, we showed that Lyces;CDKC;1 did not interact with mitotic and G1 cyclins [23].
• Flow cytometry indicated that the camptothecin-induced apoptosis is not associated with G1 arrest [24].

References