Disease relevance of CRABP2

• The up-regulation of cellular retinoic acid binding protein-II (CRABP-II) has been invoked as an important mechanism of clinically acquired resistance to all-trans retinoic acid (RA) therapy in acute promyelocytic leukemia (APL) [1].
• Differential effects of 9-cis and all-trans retinoic acid on the induction of retinoic acid receptor-beta and cellular retinoic acid-binding protein II in human neuroblastoma cells [2].
• Measured cross-peak volumes for CRABP-II bound retinoic acid were well predicted by a single, static conformational having a 6-s torsion angle of -60 degrees skewed from a cis conformation [3].
• Lack of mutations in LMNA, its promoter region, and the cellular retinoic acid binding protein II (CRABP II) in HIV associated lipodystrophy [4].
• Expression and functional influence of cellular retinoic acid-binding protein II in renal cell carcinoma [5].

High impact information on CRABP2

• Two cooperating retinoic acid response elements (RAREs) in the cellular retinoic acid-binding protein II (CRABPII) gene mediate differential transcriptional transactivation by retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in P19 embryonal carcinoma cells [6].
• Consistent with these results, 9-cis RA increases CRABPII mRNA levels more efficiently than all-trans RA [6].
• Using all-trans and 9-cis RA, which differentially activate RARs and RXRs, and RAR and RXR dominant-negative mutants, RAR-RXR heterodimers bound to RARE1 and RARE2 are shown to be responsible for CRABPII promoter transactivation, arguing against a unique DR spacing specifying recognition by RARs [6].
• All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs [6].
• Ultraviolet irradiation caused a near-total loss of retinoic acid induction of two RAR/RXR target genes, cellular retinoic acid binding protein-II and RA 4-hydroxylase, but did not affect 1,25-dihydroxyvitamin D3 induction of the vitamin D receptor/RXR-regulated gene vitamin D 24-hydroxylase [7].

Chemical compound and disease context of CRABP2

• Cellular Retinoic Acid-Binding Protein II Is a Direct Transcriptional Target of MycN in Neuroblastoma [8].
• Human breast cancer cell lines expressing the estrogen receptor alpha (ERalpha), all-trans-retinoic acid (ATRA) receptor alpha (RARalpha) and cellular retinoic acid binding protein II (CRABPII) genes are sensitive to ATRA-mediated growth inhibition [9].
• Retinoid signalling and gene expression in neuroblastoma cells: RXR agonist and antagonist effects on CRABP-II and RARbeta expression [10].
• 9-cis-retinoic acid selectively activates the cellular retinoic acid binding protein-II gene in human neuroblastoma cells [11].
• The RXR-homodimer antagonist, LG100754, inhibited the induction of CRABP-II mRNA in SH-SY5Y neuroblastoma cells by 9-cis RA or the RXR-specific agonist LGD1069, but had no effect when used with all-trans RA [10].

Biological context of CRABP2

• 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 [12].
• These differences coincide well with nearby amino acid substitutions in the recently reported X-ray structures of crystalline CRABP-I and CRABP-II and may assist rational design of selective ligands [3].
• Localization to 1q was confirmed by hybridization of a hCRABP-II cDNA clone against a human-mouse hybrid cell line containing a t(1;6)(q21;q13)) translocation chromosome [13].
• Cellular retinoic acid-binding protein II: a coactivator of the transactivation by the retinoic acid receptor complex RAR.RXR [14].
• CONCLUSIONS: We were able to demonstrate a downregulation of CRABP-II expression in primary RCC tumor samples compared to the corresponding normal kidney tissue [5].

Anatomical context of CRABP2

• In contrast, CRABP-II was consistently induced by RA in dermal, but not in lung fibroblasts [15].
• CRABP-II was up-regulated by agents that induce keratinocyte differentiation, and inhibited by prolonged exposure to high concentrations of RA [15].
• These results indicate that RA-induced CRABP-II mRNA accumulation is primarily localized to spinous and granular layers in epidermis, and in superficial dermis [16].
• RA induced accumulation of CRABP-II transcripts throughout the epidermis, dermal fibroblasts, and endothelial cells as determined by in situ hybridization [16].
• Northern blot analysis showed CRABP II mRNA level was only slightly reduced by addition of 10(-6) or 10(-5) M RA to cultures of neonatal foreskin-derived fibroblasts, as was the CRABP I mRNA level in cultured human gut epithelial cells [17].

Associations of CRABP2 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) [18].
• RAR-beta and CRABP II mRNA was induced by both all-trans and 9-cis retinoic acid in SH SY 5Y cells [2].
• In contrast, expression of CRABP II mRNA by cultured neonatal keratinocytes was strongly downregulated by RA [17].
• Biologic activity was shown by the induction of cellular retinoic acid-binding protein type 2 (CRABP 2) mRNA and protein; the rank order for CRABP-2 increase was retinoic acid > retinaldehyde > 9 cis retinoic acid > retinol > beta carotene [19].
• GST-CRABP II bound all trans-retinoic acid with high affinity (Kd 14.2 +/- 6.5 nM), but 9-cis-retinoic acid bound poorly [20].

Regulatory relationships of CRABP2

• RAR- and RXR-specific ligands used together induced CRABP-II and RARbeta as effectively as 9-cis RA [10].
• 9cRA exhibited a slightly weaker activity overall than atRA in inhibiting cell proliferation, inducing cellular retinoic acid binding protein II (CRABP II) mRNA levels and upregulating cytokeratin 19 expression [21].

Other interactions of CRABP2

• The extensive data assembled in this survey identified potential targets of carcinogenesis, for example the CRABP2 and GATA3 transcription factor genes [22].
• Mutation screening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no disease-associated mutations [23].
• Constitutive expression of cellular retinoic acid binding protein II and lack of correlation with sensitivity to all-trans retinoic acid in acute promyelocytic leukemia cells [1].
• Cellular localization of mRNA for cellular retinoic acid-binding protein II and nuclear retinoic acid receptor-gamma 1 in retinoic acid-treated human skin [16].
• Expression of estrogen receptor alpha, retinoic acid receptor alpha and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells [9].

Analytical, diagnostic and therapeutic context of CRABP2

• To test this hypothesis, we used quantitative reverse transcription-PCR and fast performance liquid chromatography procedures to examine the levels of CRABP-II mRNA and RA binding activity in APL patient samples [1].
• After 45 days of remission induction therapy on Eastern Cooperative Oncology Group protocol E2491, CRABP-II mRNA was modestly increased from day 0 values in patients treated with either RA (median increase, 0.41) or chemotherapy (median increase, 0.56), and there was no significant difference between the two treatment groups (P = 0.91) [1].
• MATERIALS AND METHODS: We used the real-time RT-PCR methodology to investigate CRABP-II expression in 12 RCC samples and corresponding normal kidney tissue [5].
• PCR analysis of total mRNA from RA-treated cells showed a biphasic early induction of CRBP-I, CRABP-II, and RARgamma2 genes [24].
• Using this approach and immunohistochemistry we could demonstrate a down-regulation of cellular retinoic acid binding protein 2 (CRABP2) mRNA and protein in carcinoma cells compared to normal glandular cells [25].

References