The cellular retinoic acid binding proteins

Donovan, M. Kathleen; Olofsson, Birgitta; Gustafson, Anne-Lee; Dencker, Lennart; Eriksson, Ulf J.

doi:10.1016/0960-0760(95)00092-e

Cited by 91 publications

(51 citation statements)

References 40 publications

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“…Of the two CRABP isoforms, CRABP1 is expressed in almost all tissues, where it binds RA at high affinity (Fiorella et al, 1993), and moderates cellular response to RA by facilitating catabolism and/or by sequestering RA, rendering it unavailable to nuclear receptors (Donovan et al, 1995). However, CRABP1 is not directly involved in the retinoid receptor-mediated RAsignaling pathway (Venepally et al, 1996), and has no effect on the RA-induced transcriptional activity of retinoic acid receptors (Dong et al, 1999).…”

Section: Association Between Crabp1 Expression and Clinicopathologic mentioning

confidence: 99%

Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma

et al. 2007

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Epigenetic alterations and the resulting inactivation of tumor suppressor genes often contribute to the development of various cancers. To identify novel candidates that may be silenced by aberrant methylation in esophageal squamous-cell carcinoma (ESCC), we analysed ESCC cell lines by a recently developed method known as bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA), and selected candidates through BAMCA-assisted strategy. In the course of this program, we identified frequent CpG methylationdependent silencing of the gene encoding cellular retinoic acid binding protein 1 (CRABP1) in our panel of ESCC cell lines. Expression of CRABP1 mRNA was restored in gene-silenced ESCC cells after treatment with 5-aza 2 0 -deoxycytidine. The DNA methylation status of the CRABP1 CpG island with clear promoter activity correlated inversely with expression of this gene. CpG methylation of CRABP1 was frequently observed in primary ESCC tissues as well. Restoration of CRABP1 expression in ESCC cells lacking the protein reduced cell growth by inducing arrest at G 0 -G 1 , whereas knockdown of the gene in cells expressing CRABP1 promoted cell growth. 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. These results indicate that CRABP1 appears to have a tumorsuppressor function in esophageal epithelium, and its epigenetic silencing may play a pivotal role during esophageal carcinogenesis. Its expression status in biopsies or resected tumors might serve as an index for identifying ESCC patients for whom combined therapeutic modalities would be recommended.

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Section: Association Between Crabp1 Expression and Clinicopathologic mentioning

confidence: 99%

Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma

et al. 2007

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“…CRABP I binds all-trans retinoic acid (RA), an active metabolite of vitamin A, which controls a variety of cellular processes including differentiation, proliferation, and apoptosis in vertebrates from the embryonic stage throughout the entire adult life [2]. Despite being an important modulator of the pleiotropic effects of RA, CRABP I does not appear to interact directly with the nuclear retinoic acid receptor [3], and is likely to function as a sequestering agent rather than a transport protein [4]. This 15.5 kDa protein contains 136 residues that form two five-stranded ␤-sheets (Figure 1).…”

Section: Ellular Retinoic Acid Binding Protein I (Crabp I)mentioning

confidence: 99%

“…Endogenous concentration of CRABP I in tissues expressing this protein (e.g., limb buds, neuronal tissues, etc.) is estimated to be in the range 1-10 M, a level that corresponds°to°ca.°10 7 -10 8°p rotein°molecules°per°cell° [4]. The°ESI°mass°spectrum°of°a°2°M°aqueous°solution°of apo-CRABP I contains only ion peaks corresponding to the°monomeric°state°of°the°protein°(Figure°2a).°The charge state distribution is narrow, and the average number of charges accommodated by the protein ions is low, indicating that the protein is compactly folded in solution.°A°noticeable°change°in°the°spectrum°occurs when the protein concentration is increased ten-fold to 20°M°(Figure°2b).°A°new°set°of°ion°peaks°appears°in m/z range 2300 -2800.…”

Section: Crabp I Association In Solutionmentioning

confidence: 99%

Transient structural disorder as a facilitator of protein-ligand binding: Native H/D exchange—Mass spectrometry study of cellular retinoic acid binding protein I

Kaltashov

2005

J. Am. Soc. Mass Spectrom.

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Binding of all-trans Retinoic Acid (RA) to Cellular Retinoic Acid Binding Protein I (CRABP I) does not result in significant changes of the protein tertiary structure, even though the binding site is inaccessible in a static apo-protein conformation. One of the proposed scenarios for the protein-ligand binding process invokes the notion of a flexible portal region adjacent to the binding site, while another model suggests that the requisite dynamic events are induced by dimerization of the apo-protein in solution. In this work, RA binding to CRABP I is studied in dilute solutions (low micro-molar range), where no dimer and/or oligomer formation occurs. Modulation of backbone dynamics within various segments of the protein by its ligand is assessed using a combination of hydrogen exchange, electrospray ionization mass spectrometry, and collision-induced dissociation of protein ions in the gas phase. Consistent with the portal model of ligand entry, several protein segments (most of them containing residues making hydrophobic contacts to RA in the holo-form of the protein) are flexible in the absence of the ligand. At the same time, the two segments containing arginine residues forming a salt bridge with RA form the least flexible region in the apo-form of the protein. Although the presence of RA in solution reduces flexibility of all protein segments, the largest effect is observed within four strands that form one of the two ␤-sheets enveloping a cavity which houses the ligand-binding site. These results are consistent with a model in which ligand binding occurs through a partially unstructured state of the protein with unobstructed access to the ligand-binding site. This intermediate (whose core is formed by the two stable arginine-containing strands) corresponds to a relatively low-energy local minimum on the apo-protein energy surface and is frequently sampled under native conditions. (J Am Soc Mass Spectrom 2005, 16, 869 -879)

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“…It has been suggested that CRBP and CRABP regulate the availability of RA in vivo: for example, the retinol dehydrogenase activity of SDRs is activated in the presence of CRBPI in mice (Yost et al, 1988), while CRABPII mediates the transport of RA to the nucleus (Donovan et al, 1995) and is involved in regulating the transcriptional activity of RA signaling (Delva et al, 1999).…”

Section: An Overview Over the Ra Signaling Cascadementioning

confidence: 99%

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

Campo-Paysaa

Marlétaz

Laudet

et al. 2008

Genesis

115

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Summary: Retinoic acid (RA) is a vitamin A-derived morphogen important for axial patterning and organ formation in developing vertebrates and invertebrate chordates (tunicates and cephalochordates). Recent analyses of genomic data have revealed that the molecular components of the RA signaling cascade are also present in other invertebrate groups, such as hemichordates and sea urchins. In this review, we reassess the evolutionary origins of the RA signaling pathway by examining the presence of key factors of this signaling cascade in different metazoan genomes and by comparing tissue-specific roles for RA during development of different animals. This discussion of genomic and developmental data suggests that RA signaling might have originated earlier in metazoan evolution than previously thought. On the basis of this hypothesis, we conclude by proposing a scenario for the evolution of RA functions during development, which highlights functional gains and lineage-specific losses during metazoan diversification. genesis 46:640-656,

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The cellular retinoic acid binding proteins

Cited by 91 publications

References 40 publications

Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma

Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma

Transient structural disorder as a facilitator of protein-ligand binding: Native H/D exchange—Mass spectrometry study of cellular retinoic acid binding protein I

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

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