Disease relevance of Rbp1

• They do not present any of the congenital abnormalities related to retinoic acid (RA) deficiency, indicating that CRBPI is not indispensable for RA synthesis [1].
• Cellular retinol (CRBP) and retinoic acid binding proteins (CRABP) were measured in normal (C57Bl) and Murine Mammary Tumor Virus (MuMTV)-induced murine mammary tumor cells (C57BlfRIII) grown in monolayer culture [2].
• A method for saturation analysis of cellular retinoic acid and retinol binding proteins, CRABP and CRBP, respectively, in cultured cells and human tumor samples, and its application to a retinoic acid resistant subline of the human neuroblastoma LA-N-5 cell line is described [3].
• Similarly, the level of the cellular retinol binding protein (CRBP) was greatly reduced in the hepatoma tissue [4].

High impact information on Rbp1

• CRABP was detected in 10 and CRBP in 3 of the 11 tested cell lines [5].
• The levels of CRBP and CRABP were in the ranges 15-3,400 and 4-1,290 pmol per 10(9) cells, respectively, as determined by sucrose gradient centrifugation [5].
• The gene encoding cellular retinol (ROL, vitA)-binding protein type I (CRBPI) has been inactivated [1].
• However, CRBPI deficiency results in an approximately 50% reduction of retinyl ester (RE) accumulation in hepatic stellate cells [1].
• Cellular retinol-binding protein I is essential for vitamin A homeostasis [1].

Biological context of Rbp1

• Deletion mapping of a CRBPI promoter--chloramphenicol acetyltransferase reporter gene construct localized this element to a 259 bp restriction fragment located approximately 1 kb upstream from the transcription start-site [6].
• Similarly, expression of CRBP I in the choroid plexuses, which develop abnormally in conditions of vitamin A deficiency, is consistent with observations indicating that this binding protein mediates the synthesis of RA in tissues requiring high levels of RA for their normal developmental programme [7].
• Second, the specific expression of CRABP and CRBP in numerous developing tissues indicates that these proteins may perform specific functions during morphogenesis of a broad variety of embryonic structures [8].
• Spatial and temporal pattern of expression of the cellular retinoic acid-binding protein and the cellular retinol-binding protein during mouse embryogenesis [8].
• We report here the gene expression patterns, as revealed by in situ hybridisation, of the retinoic acid receptors alpha, beta and gamma (RAR-alpha, -beta and -gamma), and the cellular binding proteins for retinol and retinoic acid (CRBP, CRABP) in non-neural tissues of mouse embryos during the period of organogenesis [9].

Anatomical context of Rbp1

• The RARbeta2gamma2 retinal pigment epithelium (RPE) cells display histological and/or ultrastructural alterations and/or fail to express cellular retinol binding protein I (CRBPI) [10].
• It is therefore unlikely that CRABPs and CRBPI are directly involved in development of the cochlea and hair cell differentiation [11].
• The caudate/putamen of the developing brain showed strong CRBP I-IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I-IR neurons [12].
• Morphological observations of CRBPI- and CRABPI/CRABPII-null mutant fetus at 18.5 dpc do not show any structural modification at the level of the organ of Corti [11].
• (iii) In the craniofacial region, CRABP transcripts were found in the mesenchyme of the frontonasal mass and mandible, while CRBP transcripts were found in the mesenchyme of the nasolachrymal duct and surrounding the auditory vesicle [8].

Associations of Rbp1 with chemical compounds

• A specific cis-acting element responsible for retinoic acid (RA) inducibility of the mCRBPI promoter was identified and characterized [6].
• The control of CRBPI gene transcription by RA-RAR complexes interacting with the RARE characterized here may correspond to a feedback mechanism important in regulating retinoid metabolism and action [6].
• Interestingly, the expression of the three genes, RAR-beta, CRABP II and CRBP I, is induced by retinoic acid, which suggests a link between the synthesis of RA from retinol and the control of expression of subsets of RA-responsive genes [13].
• 3) Induction of CRABP mRNA by RA was blocked by the protein synthesis inhibitor cycloheximide, whereas induction of CRBP mRNA was not [14].
• Western analysis revealed that CRBP protein was elevated 3.2-fold (p < 0.01, n = 6) and 3.0-fold (p < 0.01, n = 6) after all-trans retinoic acid treatment of human skin in vivo for 24 and 96 h, respectively, compared with vehicle- and sodium lauryl sulfate-treated skin [15].

Physical interactions of Rbp1

• Monoclonal antibodies to nuclear retinoid receptors demonstrated that predominantly retinoic acid receptor-alpha/retinoid X receptor-alpha heterodimers bound to the CRBP retinoic acid response element [15].

Regulatory relationships of Rbp1

• By 15.5 dpc, CRBP I expression is down-regulated in the yolk sac where CRBP II becomes strongly expressed [16].
• Most mesenchymal cells of the limbs and craniofacial structures did not express detectable levels of CRBP I but instead expressed cellular retinoic acid-binding protein I (CRABP I) [17].
• A retinoic acid response element from the rat CRBPI promoter is activated by an RAR/RXR heterodimer [18].
• Our results indicate that RA produced by the CRBP I-expressing 'glia-like' cells may act as a neurotrophic factor for the CRABP I-expressing immature olfactory axons [19].

Other interactions of Rbp1

• RAR-beta and CRABP II, which are both RA-inducible, were coexpressed with CRBP I in the choroid plexus and in many other sites, perhaps reflecting the fact that all three genes are RA-inducible [7].
• No CRABP or CRBP transcripts were observed in the auditory receptors [11].
• A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter [6].
• Opposing actions of cellular retinol-binding protein and alcohol dehydrogenase control the balance between retinol storage and degradation [20].
• The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers [21].

Analytical, diagnostic and therapeutic context of Rbp1

• As a step towards understanding the possible function for CRABP and CRBP in morphogenesis, we have used in situ hybridization to analyze their expression during mouse development [8].
• As revealed by immunohistochemistry using antibodies to cellular retinol-binding protein I (CRBP I), retinol accumulates in regions of the embryo expressing CRBP I [17].
• The cellular retinol binding protein II gene. Sequence analysis of the rat gene, chromosomal localization in mice and humans, and documentation of its close linkage to the cellular retinol binding protein gene [22].
• After transfections of CRABP and CRBP into cultured cells, immunofluorescence analyses again revealed cytoplasmic restriction only for CRABP, with a pronounced punctate appearance [23].
• Specificity of phosphorylation of the retinoid-binding proteins was confirmed by polyacrylamide gel electrophoresis and subsequent autoradiography of the assay mixture as well as by a concentration-dependent, Ca+2, and phosphatidylserine sensitivity of the phosphorylation of both apo-cRBP and apo-cRABP [24].

References