Disease relevance of Diamazo

• PC-cell derived growth factor (PCDGF) is an 88-kDa growth factor originally purified from the highly tumorigenic teratoma PC cell line and corresponds to the epithelin/granulin precursor [1].
• We identified granulin as a cyclin T1-interacting protein that represses expression from the HIV-1 promoter in transfected cells [2].
• The differential expression pattern, tissue distribution, and implication of this glioma-associated molecule in growth regulation suggest a potentially important role for granulin in the pathogenesis and/or malignant progression of primary brain neoplasms [3].
• The current study found zinc associated with both granulosis virus nucleocapsids and granulin by atomic absorption analysis [4].
• Substitution of granulin from the Trichoplusia ni granulosis virus (TnGV) for polyhedrin of the Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV) yielded a few very large (2 to 5 micron) cuboidal inclusions in the cytoplasm and nucleus of infected cells [5].

High impact information on Diamazo

• Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468 [1].
• The granulin/epithelin protein motif has an unusual structure consisting of a parallel stack of beta-hairpins stapled together by six disulphide bonds [6].
• Epithelin 1, which is probably identical to rat leukocyte granulin, exhibits proliferative and antiproliferative effects on epithelial cells in vitro [7].
• Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains [7].
• The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription [2].

Chemical compound and disease context of Diamazo

• Using in vitro mutagenesis assays, we showed that each one of the three cysteine residues located within the cysteine-rich domain of the CAEV Tat protein is essential for the binding of Tat to both the Notch2 and the epithelin/granulin protein [8].
• Reactivity of amino groups, phenoxy groups of tyrosine residues and some other charged groups of Tricoplusia ni granulosis virus granulin, which had rigid subunit structure abundant in beta-configuration, was investigated [9].

Biological context of Diamazo

• Binding of granulin to P-TEFb inhibited the phosphorylation of a CTD peptide [2].
• Granulins DE and E repress transcription from the HIV-1 LTR and gene expression from the viral genome, raising the possibility of developing granulin-based inhibitors of viral infection [10].
• In this study, goldfish granulin was one of the most commonly identified transcripts in the differential cross-screening of macrophage cDNA libraries and was preferentially expressed in proliferating macrophages [11].
• These results indicate that goldfish granulin is a growth factor that positively modulates cell proliferation at distinct junctures of macrophage differentiation [11].
• The existence of a large molecular mass precursor for granulin or epithelin has been predicted based upon recently cloned cDNAs encoding these biomolecules within a 63.5-kDa protein with putative glycosylation sites [12].

Anatomical context of Diamazo

• Recombinant goldfish granulin induced a dose-dependent proliferative response of goldfish macrophages that was inversely related to the myeloid differentiation stage of the cells studied [11].
• The present results indicate that PCDGF is a potential precursor for epithelin and/or granulin, that this 88-kDa protein is secreted and glycosylated, and that it can function as a mitogen for 3T3 cells as well as an autocrine growth factor for PC cells [12].
• Since one hallmark of embryo development is the formation of an epithelium, the trophectoderm, we tested the hypothesis that one such embryo-derived growth factor is acrogranin (epithelin/granulin precursor), a factor that possesses growth-regulatory activities principally toward epithelial cells [13].
• Taken together, these results indicate that the intermediate of RD21 was accumulated in the vacuoles as an aggregate, and then slowly matured to make a soluble protease by removing the granulin domain during leaf senescence [14].
• Thirty-six of these residues (78.3%) were identical to those of a recently cloned human neutrophil peptide of unknown function and belonging to the granulin family [15].

Associations of Diamazo with other chemical compounds

• Granulin bound to the histidine-rich domain of cyclin T1, which was recently found to bind to the CTD, but not to cyclin T2 [2].
• Unlike other members of the papain family, RD21 has a C-terminal extension sequence composed of two domains, a 2-kD proline-rich domain and a 10-kD domain homologous to animal epithelin/granulin family proteins [14].
• Induction of granulin precursor gene expression by estrogen treatment in neonatal rat hypothalamus [16].
• Our previous research has demonstrated that androgen treatment during the perinatal period increases granulin (grn) precursor mRNA levels in the neonatal rat hypothalamus [16].
• Furthermore, the primary structures of guinea pig and mouse acrogranins, deduced from the cDNA sequences, reveal that this glycoprotein is a cysteine-rich molecule with a motif that is tandemly repeated seven times, very similar to that of the human epithelin/granulin precursor [17].

Gene context of Diamazo

• Sequencing the region surrounding the human alphaIIb locus showed the Granulin gene approximately 18 kb downstream to alphaIIb, and the KIAA0553 gene approximately 5.7 kb upstream [18].
• Phylogenetic trees of the granulovirus genes egt, granulin, pk-1 and me53 were constructed using maximum parsimony and distance analyses [19].
• Somatostatin-, vasoactive intestinal peptide-, and granulin-like peptides isolated from intestinal extracts of goldfish, Carassius auratus [20].
• Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) [21].
• Granulin and granulin repeats interact with the Tat.P-TEFb complex and inhibit Tat transactivation [10].

Analytical, diagnostic and therapeutic context of Diamazo

• Northern blot and real-time PCR analyses indicated that goldfish granulin was expressed only in the hematopoietic tissues of the goldfish, specifically the kidney and spleen, and in activated peripheral blood mononuclear cells [11].
• The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search [22].
• The granulin gene region of Cryptophlebia leucotreta granulosis virus: sequence analysis and phylogenetic considerations [23].
• T. ni larval bioassays showed that a factor, present in the TnGV granulin or AcMNPV polyhedrin, enhanced the infectivity of AcMNPV [24].
• Comparison of mRNA levels by semi-quantitative RT-PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1--an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development [25].

References