Transfer of retinoic acid from its complex with cellular retinoic acid-binding protein to the nucleus

Takase, Sachiko; Ong, David E.; Chytil, Frank

doi:10.1016/0003-9861(86)90591-6

Cited by 168 publications

(69 citation statements)

References 19 publications

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“…Intracellular RA may also bind to CRABP2, which facilitates delivery to the nucleus (12,34), where it activates RAR transcriptional regulation of target genes (35). In our cohort, the four babies who were homozygous for the CRABP2 rs12724719A variant had substantially increased levels of cord blood RA compared with newborns who were homozygous for the wildtype G allele (141.3 versus 32.3 nmol/L, respectively).…”

Section: Discussionmentioning

confidence: 78%

Newborn Serum Retinoic Acid Level Is Associated With Variants of Genes in the Retinol Metabolism Pathway

et al. 2010

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Retinoic acid (RA) is a critical regulator of gene expression during embryonic development. In rodents, moderate maternal vitamin A deficiency leads to subtle morphogenetic defects and inactivation of RA pathway genes causes major disturbances of embryogenesis. In this study, we quantified RA in umbilical cord blood of 145 healthy full-term Caucasian infants from Montreal. Sixty seven percent of values were Ͻ10 nmol/L (84 were Ͻ0.07 nmol/L) and 33% had moderate or high levels. Variation in RA could not be explained by parallel variation in its precursor, retinol (ROL). However, we found that the (A) allele of the rs12591551 single nucleotide polymorphism (SNP) in the ALDH1A2 gene (ALDH1A2 rs12591551(A) ), occurring in 19% of newborns, was associated with 2.5-fold higher serum RA levels. ALDH1A2 encodes retinaldehyde dehydrogenase (RALDH) 2, which synthesizes RA in fetal tissues. We also found that homozygosity for the (A) allele of the rs12724719 SNP in the CRABP2 gene (CRABP2 rs12724719(A/A) ) was associated with 4.4-fold increase in umbilical cord serum RA. CRABP2 facilitates RA binding to its cognate receptor complex and transfer to the nucleus. We hypothesize that individual variation in RA pathway genes may account for subtle variations in RAdependent human embryogenesis. (Pediatr Res 67: 598-602, 2010)

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Section: Discussionmentioning

confidence: 78%

Newborn Serum Retinoic Acid Level Is Associated With Variants of Genes in the Retinol Metabolism Pathway

et al. 2010

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“…It is usually proposed that CRABPs serve to solubilize and protect their ligand in cytosol and that they transport RA between different cellular compartments (2). It was suggested, for example, that CRABPs act to deliver their ligand to the nucleus (8). Indeed, it was recently demonstrated that both CRABP isoforms are present not only in cytosol but also in the nuclei of cells (9).…”

mentioning

confidence: 99%

Distinct Roles for Cellular Retinoic Acid-binding Proteins I and II in Regulating Signaling by Retinoic Acid

Dong

Ruuska

Levinthal

et al. 1999

Journal of Biological Chemistry

316

275

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“…The possible function as down-regulator suggests a mechanism whereby the response of the cells to retinoic acid can be modulated by the concentration of CRABP in the cytosol. Furthermore, an involvement of this protein in translocation of retinoic acid to the nucleus with additional protection against degradation is discussed (Takase et al, 1986;Napoli et al, 1991).…”

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confidence: 99%

In vivo biological activity of retinoids partially correlates to their affinity to recombinant retinoic‐acid receptor α and recombinant‐cellular retinoic‐acid‐binding protein I

Keidel

Szardenings

Mueller

1993

European Journal of Biochemistry

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Several known and some new retinoids were synthesized and their in vivo activity was investigated by an assay, based on induction of alkaline phosphatase in P19 teratocarcinoma cells, human prostate carcinoma cells and primary cultures of neonatal rat heart cells. The assay used in this study was found to be reproducible and useful for rapid screening of retinoids for biological activity. Two newly synthesized compounds exhibit high biological activity. The biological potency of the compounds was compared to their ability to bind to recombinant retinoic-acid receptor a and to cellular retinoic-acid-binding protein I determined by Charsorb-binding assay. mRNA of both retinoic-acid-binding proteins could be detected in the three cell lines investigated. As expected from the number of different retinoic-acid receptors, the results suggest that retinoids do not need to bind retinoic-acid receptor a nor cellular retinoic-acid-binding protein I in order to exhibit biological activity, but most retinoids investigated show a clear correlation between binding to these proteins and their biological activity.

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Transfer of retinoic acid from its complex with cellular retinoic acid-binding protein to the nucleus

Cited by 168 publications

References 19 publications

Newborn Serum Retinoic Acid Level Is Associated With Variants of Genes in the Retinol Metabolism Pathway

Newborn Serum Retinoic Acid Level Is Associated With Variants of Genes in the Retinol Metabolism Pathway

Distinct Roles for Cellular Retinoic Acid-binding Proteins I and II in Regulating Signaling by Retinoic Acid

In vivo biological activity of retinoids partially correlates to their affinity to recombinant retinoic‐acid receptor α and recombinant‐cellular retinoic‐acid‐binding protein I

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