Disease relevance of Ybx1

• At 12 and 18 mo after initiation, most grossly visible hepatocellular tumors retained induced expression of glutathione S-transferase subunits Yf, Ya and Yb1, but 63% of the carcinomas, 88% of the primary metastatic carcinomas and 94% of the pulmonary metastases were deficient in Yb2 expression [1].
• Of additional interest and again like Y-box proteins, SSBP-1 is a member of a family of SSBPs that interact with RNA and are important in RNA processing, can interact with the promoter of retroviruses, and can interact with a gene linked to growth and DNA replication, c-myc [2].
• Expression of Yb1 glutathione S-transferase using a baculovirus expression system [3].
• The expressed Yb1 subunits are assembled into a dimer as purified from sonicated E. coli crude extracts [4].
• Immunoblot assay showed that, accompanying the increase in hepatic GST activity, GO, DADS, DAS (80 mg/kg body weight) and DATS increased the expression of GST Ya, Yb1 and Yc proteins [5].

High impact information on Ybx1

• Finally, we observed a correlation between the expression of PTP1B and that of YB-1 in cancer cell lines and an animal model of type II diabetes [6].
• Our data reveal an important role for YB-1 as a regulator of PTP1B expression, and further highlight PTP1B as a critical regulator of insulin- and cytokine-mediated signal transduction [6].
• These findings strongly support a multifunctional role for Cbfa factors in regulating gene expression, not only as simple transcriptional transactivators but also by facilitating modifications in promoter architecture and chromatin organization [7].
• Significantly, related to these losses in transcriptional activity, mutation of the three Cbfa sites results in altered chromatin structure as reflected by loss of DNase I-hypersensitive sites at the vitamin D response element and over the proximal tissue-specific basal promoter [7].
• The functional significance of each Cbfa element was addressed by mutating individual or multiple Cbfa sites within the context of the -1.1-kb rOC promoter fused to a chloramphenicol acetyltransferase reporter gene [7].

Biological context of Ybx1

• Although the human r2 sequence specifically interacts with AP2 (Mol Cell Biol 10: 6524-6532, 1990), there is no clear evidence for the presence of a canonical YB-1 binding site (Y-box) within this sequence [8].
• Y-box proteins are DNA- and RNA-binding proteins and control specific gene expression at both transcriptional and translational levels [9].
• A deduced amino acid sequence of the protein was very similar to that of several other Y-box proteins, and we termed the protein rBYB1 (rat brain Y-box protein 1). rBYB1 was found to be considerably expressed in the cytoplasm of pre- and early postnatal brains, and then decreased to adult levels with brain development [9].
• Transfection of mouse promoter deletional constructs into expressing and non-expressing CFTR murine cell lines revealed that the Pu.Py stretch and the Y-box act, respectively, as negative and positive elements of basal transcription that confer no apparent tissue specificity [10].
• Over the protein coding region of the Yb1 and Yb2 cDNA clones there is an 84% nucleotide sequence homology, whereas the 3' untranslated regions are only 32% homologous [11].

Anatomical context of Ybx1

• Particularly in germ cells, it has been reported that Y-box proteins bind to paternal or maternal mRNAs to form mRNPs, mask them from translation and control cell maturation [9].
• Linker scanning analyses of the S14 promoter showed that an SRE at -139/-131 base pairs (bp) binding SREBP-1c and a Y-box at -104/-99 bp binding NF-Y are indispensable for both T(3)- and SREBP-1c-mediated induction of S14 promoter activity in rat primary hepatocytes [12].
• Treatment of rats with phenobarbital induces the level of glutathione S-transferase D in testis with no increase in the activities of glutathione S-transferases A and C. This result indicates a specific induction of the Yb2 subunit in testis, in contrast with the situation in rat liver, where phenobarbital specifically induces the Yb1 subunit [13].
• Major histocompatibility class II HLA-DR alpha gene expression in thyrocytes: counter regulation by the class II transactivator and the thyroid Y box protein [14].
• In the cytosol, a further known bile acid binding protein, the glutathione-S-transferase (G-S-T) subunit Yb1, was isolated and sequenced as binding protein for CDP and also for a further cyclopeptide, the somatostatin analogue OO8, and a linear peptide with renin-inhibiting activity, EMD 55068 [15].

Associations of Ybx1 with chemical compounds

• Highlights of both the rat and mouse promoter sequences include an extensive purine rich stretch, a Y-box motif and putative Sp1, AP1 sites [10].
• At 6 mo after initiation, altered foci and persistent nodules displayed increased immunohistochemical expression of glutathione S-transferase subunits Yf (pi-class), Ya (alpha-class) and Yb1 (mu-class) in comparison with normal or surrounding liver tissue [1].
• In contrast, the levels of subunits Yb1 and Yc2 diminished to approximate control levels within 7 days after a single dose of oltipraz [16].
• In contrast, dexamethasone preferentially induced Yb1, Yb2, and Ya2, while two other inducers of liver drug metabolism, isoniazid and clofibrate, were less effective with respect to GST induction [17].
• Our results clearly show that the Yb1 and Yb2 mRNAs are elevated approximately 5-6-fold by phenobarbital administration; whereas the Yc mRNA is only modestly elevated by this xenobiotic [11].

Other interactions of Ybx1

• Y-box protein-1 is the crucial mediator of antifibrotic interferon-gamma effects [18].

Analytical, diagnostic and therapeutic context of Ybx1

• Northern blot analysis of total liver RNA using probes specific for individual GSTs belonging to classes alpha (GSTs Ya1, Ya2, Yc), mu (GSTs Yb1, Yb2, Yb3), pi (GST Yp), and GSTms demonstrated the expression in liver of all but Yp mRNA [17].
• Quantitative HPLC analyses of GST subunits 24 h after 2 or 7 daily administrations of oltipraz showed that the levels of subunits Yb1, Yp, Yc2, and Ya2 were increased with maximum elevations of 5.6-, 11.1-, 6.4-, and 10.4-fold, respectively [16].
• In the present study, the distribution of Ya and Yc subunits from the alpha family, Yb1 and Yo subunits of the mu class, and the Yf subunit of the pi class were examined with light microscope immunocytochemistry in Bouin-fixed, paraffin-embedded tissue of different regions of the cauda epididymidis and vas deferens [19].
• A maximal reduction in GST Ya, Yb1/2, and Yc1 mRNA levels was also noted at 18 hr after treatment with GdCl3, followed by a gradual return to levels in untreated rats at later time points [20].
• Immunolocalization of the Yb1 subunit of glutathione S-transferase in the adult rat epididymis following orchidectomy and efferent duct ligation [21].

References