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Cellular Retinoic Acid Binding Proteins: Genomic and Non-genomic Functions and their Regulation

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Book cover The Biochemistry of Retinoid Signaling II

Part of the book series: Subcellular Biochemistry ((SCBI,volume 81))

Abstract

Cellular retinoic acid binding proteins (CRABPs) are high-affinity retinoic acid (RA) binding proteins that mainly reside in the cytoplasm. In mammals, this family has two members, CRABPI and II, both highly conserved during evolution. The two proteins share a very similar structure that is characteristic of a “β-clam” motif built up from10-strands. The proteins are encoded by two different genes that share a very similar genomic structure. CRABPI is widely distributed and CRABPII has restricted expression in only certain tissues. The CrabpI gene is driven by a housekeeping promoter, but can be regulated by numerous factors, including thyroid hormones and RA, which engage a specific chromatin-remodeling complex containing either TRAP220 or RIP140 as coactivator and corepressor, respectively. The chromatin-remodeling complex binds the DR4 element in the CrabpI gene promoter to activate or repress this gene in different cellular backgrounds. The CrabpII gene promoter contains a TATA-box and is rapidly activated by RA through an RA response element. Biochemical and cell culture studies carried out in vitro show the two proteins have distinct biological functions. CRABPII mainly functions to deliver RA to the nuclear RA receptors for gene regulation, although recent studies suggest that CRABPII may also be involved in other cellular events, such as RNA stability. In contrast, biochemical and cell culture studies suggest that CRABPI functions mainly in the cytoplasm to modulate intracellular RA availability/concentration and to engage other signaling components such as ERK activity. However, these functional studies remain inconclusive because knocking out one or both genes in mice does not produce definitive phenotypes. Further studies are needed to unambiguously decipher the exact physiological activities of these two proteins.

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Abbreviations

AP2:

Activating Protein 2

COUP:

Chicken Ovalbumin Upstream Promoter

CRABP:

Cellular Retinoic Acid Binding Protein

DR:

Direct Repeat

ERK:

Extracellular Signal-Regulated MAP kinase

ESC:

Embryonic Stem Cell

GCNF:

Germ Cell Nuclear Factor

LRH-1:

Liver Receptor Homologue-1

PPAR:

Peroxisome Proliferator Activated Receptor

RAR:

Retinoic Acid Receptor

RXR:

Retinoid X Receptor

RA:

Retinoic Acid

SF-1:

Steroidogenic Factor 1

SP1:

Specific Protein 1

TR2:

Testis Receptor 2

TRAP220:

Thyroid hormone Receptor-Associated Protein 220

RIP140:

Receptor Interacting Protein 140

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Acknowledgements

This work was supported by NIH grants DK54733, and DK60521, the Dean’s Commitment, and the Distinguished McKnight Professorship of University of Minnesota (LNW). I thank Shawna Persaud for preparing the figures.

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Authors and Affiliations

  1. Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. SE, 55455, Minneapolis, MN, USA

    Li-Na Wei

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Correspondence to Li-Na Wei .

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  1. Tennessee State University, Nashville, Tennessee, USA

    Mary Ann Asson-Batres

  2. Functional Genomics & Cancer, Institut de Genetique et de Department Functional Genomics & Cancer, Illkirch, France

    Cecile Rochette-Egly

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Wei, LN. (2016). Cellular Retinoic Acid Binding Proteins: Genomic and Non-genomic Functions and their Regulation. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoid Signaling II. Subcellular Biochemistry, vol 81. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0945-1_6

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