Disease relevance of CRABP1

• Treatment with 5-Aza-dC alone restored CRABP1 expression in a colorectal cancer cell line, SW48 [1].
• Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells [2].
• In squamous cell carcinoma of the cervix, CRABP I was detected in cells throughout the tumor but was minimal in cells demonstrating squamous differentiation [3].
• The mRNA for CRABPI is present in untreated human neuroblastoma cells, whereas the mRNA for CRABPII is induced in cells treated with either all-trans RA or 9-cis RA [4].
• Human cellular retinoic acid-binding protein (CRABP) type I and type II were expressed in Escherichia coli from cloned cDNAs [5].
• Among 113 primary ESCC tumors, the absence of immunoreactive CRABP1 was significantly associated with de-differentiation of cancer cells and with distant lymph-node metastases in the patients [6].

High impact information on CRABP1

• Tissues of rats, humans, and other species contain soluble binding proteins with specificity for either retinol (cellular retinol-binding protein) or retinoic acid (cellular retinoic acid-binding protein) [7].
• The quality of CRABP per milligram of cytosol protein ranged from 48.3 to 426.5 fmol [8].
• Cellular retinoic acid-binding protein in human lung carcinomas [8].
• Cellular retinoic acid-binding protein (CRABP) was detected in the cytosol of 11 human non-small-cell lung cancer specimens [8].
• The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP) [9].

Chemical compound and disease context of CRABP1

• We have thus investigated the expression of nuclear retinoic acid receptors (RARs and RXRs) and cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) in endometrial adenocarcinoma of the endometrioid histological subtype [10].
• In contrast, acitretin had no significant effect on intracellular retinoid concentrations in those neuroblastoma cell lines that showed little or no induction of CRABP after RA treatment [11].
• The CRABP was (1) in much higher levels in normal epidermis than in normal dermis, (2) dramatically elevated in psoriatic plaques and in some retinoid-responsive dermatoses, and (3) up modulated by both topical and systemic administration of natural and synthetic retinoids [12].
• Human colon adenocarcinomas and adjacent non-cancerous, normal colon from the same patient were assayed for the presence and amounts of cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) by sucrose gradient analysis [13].
• Drug interaction of isotretinoin and protease inhibitors: support for the cellular retinoic acid-binding protein-1 theory of lipodystrophy [14]?

Biological context of CRABP1

• Loss of expression of MT1G and CRABP1 is accompanied by hypermethylation in the 5' regions of these genes, but methylation was not seen in other genes tested [1].
• Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma [1].
• Assignment of the genes for cellular retinoic acid binding protein 1 (CRABP1) and 2 (CRABP2) to human chromosome band 15q24 and 1q21.3, respectively, by in situ hybridization [15].
• Northern blot analysis of 12 breast cell lines showed that CRABPII mRNA content correlated with growth inhibition by RA, suggesting that this binding protein enhances cellular response to RA [16].
• Here, we investigated molecular events through which RA inhibits the growth of MCF-7 mammary carcinoma cells, focusing on the involvement of the two proteins that mediate transcriptional activation by RA, the nuclear hormone receptor retinoic acid receptor (RAR) and the cellular retinoic acid-binding protein (CRABP) II, in this process [17].

Anatomical context of CRABP1

• In both the normal stratified squamous epithelium of the exocervix and low-grade CIN, CRABP I was present predominantly in the basal layer of the epithelium [3].
• We conclude that CRABP II is the predominant CRABP in human skin, at least in the newborn period, and that it is differentially regulated in fibroblasts versus keratinocytes [18].
• Binding affinities varied according to the order brain approximately myelin approximately heart > liver > intestine > CRABP > CRBP [19].
• This study describes the pattern of expression of nuclear retinoic acid receptors (RARs and RXRs), and cellular binding proteins for retinol and retinoic acid (CRBP I, CRABP I and II), in endometrial epithelial cells [20].
• Regulation of cellular retinoic acid binding protein (CRABP II) during human monocyte differentiation in vitro [21].

Associations of CRABP1 with chemical compounds

• BHY cells expressed all of retinoid nuclear receptors (RARalpha, beta, gamma, and RXRalpha) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2) [22].
• Our data are consistent with a role for CRABP in regulating the amount of RA delivered to the nucleus [18].
• Sj-FABPc of the blood fluke of humans, Schistosoma japonicum, is a member of the FABP/P2/CRBP/CRABP family of beta-barrel cytosolic fatty-acid-binding and retinoid-binding proteins [23].
• Analysis of HMQC, HMQC-TOCSY, and 13C-TOCSY-REVINEPT on CRABP-bound (2,3,6,7,8,9,10,11,19-13C)- and (1,4,5,8,9,16, 17,18,19-13C)-all trans-retinoic acid allowed the unambiguous assignment of all labeled protons and their attached 13C resonances [24].
• The protein is a single polypeptide chain with a molecular mass of 14,600 Da, estimated by sodium dodecyl sulfate (SDS) gel electrophoresis or gel filtration, and has an isoelectric point of 4.78 (apo-CRABP, 4.82) [25].

Physical interactions of CRABP1

• Epidermoid carcinomas of the oral cavity and oropharynx from six patients were examined for the presence and amount of cellular retinol (CRBP) and cellular retinoic acid-binding (CRABP) proteins [26].

Regulatory relationships of CRABP1

• The retinoic acid-sensitive cell line HTB35 was transfected for inducible CRABP I overexpression to test the role of this protein in modulating the sensitivity to retinoic acid and radiation as well as in regulating RAR-beta 2 and cyclin D1 expression [27].
• CRABP I overexpression resulted in stimulated cyclin D1 expression indicating the dependency of this cell cycle control protein on retinoic acid metabolism [27].

Other interactions of CRABP1

• In contrast to CRABP I, CRBP was diffusely present throughout the cervical epithelium irrespective of the state of differentiation or the presence of disease [3].
• The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all-trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma [28].
• The immunolocalisation of a cellular retinoic acid-binding protein (CRABP) like antigen in normal oral mucosa showed much the same picture with strongest staining of the maturing keratinocytes of the prickle cell layers [29].
• Furthermore, we demonstrate that CRABP-II is actually the CRABP previously studied in epidermal cells by a PAGE assay (Siegenthaler & Saurat (1987) Eur. J Biochem. 166, 209-214) and whose levels are dramatically increased by retinoic acid and its analogues in human epidermis [30].
• PURPOSE: To examine the role cytoplasmic retinoic acid binding protein type 1 (CRABP I) and retinoic acid receptor beta 2 (RAR-beta 2) in mediating radiosensitization of human tumour cells in vitro by retinoic acid [27].

Analytical, diagnostic and therapeutic context of CRABP1

• The molecular cloning and expression of two CRABP cDNAs from human skin [18].
• CRBP I and CRABP I expression was confirmed by immunohistochemistry [31].
• Using quantitative real-time PCR the mRNA expression of cellular retinol-binding protein I (CRBPI) and retinoic acid-binding protein I/II (CRABPI/CRABPII) was studied in psoriatic and healthy control (=normal) skin after 4 days of occlusive RA/vehicle treatment (n=6) [32].
• Moreover, the cellular retinoic acid binding protein (CRABP) has been suggested to be involved in HAART associated lipodystrophy [33].
• RESULTS: The basal CRABP I level clearly correlated with the clonogenic survival of tumour cells and normal fibroblasts after treatment with retinoic acid and ionizing irradiation (IR) [27].

References