Disease relevance of P4HB

• By embryonic day 16 (extending through post-hatching day 26), the staining of R-cognin was specific for the ganglion cell and nerve fiber layers [1].

High impact information on P4HB

• These findings demonstrate that R-cognin differs from other cell adhesion molecules and suggest possible mechanisms for its action in cell adhesion and neuronal differentiation [2].
• Retina cognin (R-cognin) is a developmentally regulated 50-kDa protein that was isolated from chicken embryo retina cell membranes [2].
• A chicken embryo retina cDNA library was constructed in lambda gt11 vector and was screened with polyclonal R-cognin antiserum, yielding several immunoreactive clones [2].
• Protein disulfide isomerase (PDI), a catalyst of oxidative protein folding, has a variety of effects on the yield of native lysozyme during the oxidative refolding of the reduced, denatured protein [3].
• Chicken and normal human PDI proteins showed tissue- and developmental-specific enhancement of cell aggregation identical to R-cognin, and this activity was blocked by inactivation of the -WCGHC- motifs which function in disulfide exchange [4].

Chemical compound and disease context of P4HB

• Retina cognin, a cell membrane glycoprotein which mediates cell-cell recognition and adhesion in vitro, is initially present throughout the retina and becomes confined to the ganglion cell layer at 14-15 days of embryogenesis [5].

Biological context of P4HB

• Molecular cloning of a multifunctional chicken protein acting as the prolyl 4-hydroxylase beta-subunit, protein disulphide-isomerase and a cellular thyroid-hormone-binding protein. Comparison of cDNA-deduced amino acid sequences with those in other species [6].
• The results demonstrated that the known decrease in R-cognin found in the retina during the latter half of embryonic development in the chick is not uniform across the retina, but that R-cognin is preferentially retained on cells within the ganglion cell layer [1].
• Retina cognin, a cell-cell recognition protein, which may itself mediate position-dependent cell interactions in vivo exhibits a characteristic change in distribution during embryonic chick development [7].
• Thus, our results indicated that DNA methylation may not play an important role in the expression of CPH beta/PDI [8].
• Examination of 5'-end flanking sequences of exon 1 of the CPH beta/PDI gene with the methylation sensitive endonucleases, Hha I and Hpa II did not reveal any difference in erythrocyte, cornea and tendon cells [8].

Anatomical context of P4HB

• Thus, the observations are consistent with a role for R-cognin in the formation or maintenance of functional cell-cell connections within the entire retina prior to developmental day 11, or in retinal ganglion cell layer formation or stability subsequent to embryonic day 11 [1].
• Our results indicate that the CPH beta/PDI gene is methylated at the Hha I site in the 4th exon in erythrocytes whereas the same sites in tendon and cornea are hypomethylated [8].
• The basal cells of corneal epithelium express CPH beta/PDI, but the superficial cell layers of stratified corneas of 19-day-old chick embryos do not [8].

Associations of P4HB with chemical compounds

• Dependence of retina cell aggregation on disulfide exchange activity was shown by blocking that activity with the inhibitor, DTNB, or with a recombinant human PDI with the -WCGHC- motif cysteines mutated [4].
• We also show that treating R-cognin and chicken PDI with the thioreductase inhibitor 5,5'-dithio-bis (2-nitrobenzoic acid), which covalently binds to the functional cysteines of the thioreductase active sites, reduces the enhancement of cell aggregation [9].
• When reduced, denatured lysozyme (1.6 mg/ml) is passed over a PDI column in 1-2 M urea in the presence of a glutathione redox buffer, the specific activity of the recovered lysozyme is identical to that of the native enzyme and the total recovery of the applied protein is 50-65% [10].
• The action of R-cognin, a chick neural retina cell recognition glycoprotein, was investigated in vesicles of retina cell membranes [11].

Other interactions of P4HB

• Distribution of R-cognin and choline acetyltransferase in the ganglion cell layer of developing chick neural retina [5].

Analytical, diagnostic and therapeutic context of P4HB

• In vitro translation of RNA from a cDNA subclone yielded a 50-kDa protein that was recognized by R-cognin antiserum on a Western blot [2].
• The 3'-terminal partial cDNA clone for R-cognin was extended by both 5' RACE and by PCR from sequence near the 5' end of the PDI-translated region [4].
• The histological distribution of R-cognin in chick retinas was determined from embryonic day 8 through 13 wk post-hatching by indirect immunofluorescence using polyclonal anticognin [1].
• Developmental localization of retina cognin synthesis by in situ hybridization [12].
• In the present study, we examined the distribution of the chicken beta-subunit of prolyl 4-hydroxylase/protein disulfide isomerase (CPH beta/PDI) in erythrocytes, corneas and tendons of 13-, 17-, and 19-day-old chick embryos by immunohistochemistry using antibodies against CPH beta/PDI [8].

References