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Non-classical Transcriptional Activity of Retinoic Acid

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The Biochemistry of Retinoid Signaling II

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

Abstract

It has long been established that the transcriptional activity of retinoic acid (RA) is mediated by members of the nuclear receptor family of ligand-activated transcription factors termed RA receptors (RARs). More recent observations have established that RA also activates an additional nuclear receptor, PPARβ/δ. Partitioning RA between RARs and PPARβ/δ is governed by different intracellular lipid-binding proteins: cellular RA binding protein 2 (CRABP2) delivers RA to nuclear RARs and a fatty acid binding protein (FABP5) delivers the hormone from the cytosol to nuclear PPARβ/δ. Consequently, RA signals through RARs in CRABP2-expressing cells, but activates PPARβ/δ in cells that express a high level of FABP5. RA elicits different and sometimes opposing responses in cells that express different FABP5/CRABP2 ratios because PPARβ/δ and RARs regulate the expression of distinct sets of genes. An overview of the observations that led to the discovery of this non-classical activity of RA are presented here, along with a discussion of evidence demonstrating the involvement of the dual transcriptional activities of RA in regulating energy homeostasis, insulin responses, and adipocyte and neuron differentiation.

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Abbreviations

ANGLP4:

angiopoietin-like protein 4

C/EBP:

CCAAT enhancer-binding protein

CRABP:

cellular retinoic-binding protein

CRBP:

cellular retinol-binding protein

ERK:

extracellular signal-regulated kinase

FABP:

fatty acid binding protein

ILK:

integrin-linked kinase

iLBP:

intracellular lipid-binding protein

PDPK1:

3-Phosphoinositide Dependent Protein Kinase

PLIN2:

perilipin 2

PPAR:

peroxisome proliferator activated receptor

Pref-1:

preadipocyte factor 1

PTEN:

phosphatase and tensin homolog

RA:

retinoic acid

RAR:

RA receptor

VEGF:

vascular endothelial growth factor

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Acknowledgments

Work in the author’s laboratory was supported by NIH grants RO1 DK060684, RO1 DK088669, and R01 CA166955

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  1. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Noa Noy

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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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Noy, N. (2016). Non-classical Transcriptional Activity of Retinoic Acid. 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_7

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