scholarly journals EMBO Retinoids 2011: Mechanisms, Biology and Pathology of Signaling by Retinoic Acid and Retinoic Acid Receptors

2012 ◽  
Vol 10 (1) ◽  
pp. nrs.10003 ◽  
Author(s):  
Neil J. McKenna

Retinoic acid (RA) is one of the principal active metabolites of vitamin A (retinol) which mediates a spectrum of critical physiological and developmental processes. Transcriptional regulation by RA is mediated primarily by members of the retinoic acid receptor (RAR) subfamily of the nuclear receptor (NR) superfamily of transcription factors. NRs bind specific genomic DNA sequence motifs and engage coregulators and components of the basal transcription machinery to effect transcriptional regulation at target gene promoters. Disruption of signaling by retinoic acid is thought to underlie the etiology of a number of inflammatory and neoplastic diseases including breast cancer and haematological malignancies. A meeting of international researchers in retinoid signaling was convened in Strasbourg in September 2011 under the auspices of the European Molecular Biology Organization (EMBO). Retinoids 2011 encompassed myriad mechanistic, biological and pathological aspects of these hormones and their cognate receptors, as well as setting these advances in the context of wider current questions on signaling by members of the NR superfamily.

1991 ◽  
Vol 33 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Frank A.E. Kruyt ◽  
Christina E. van den Brink ◽  
Libert H.K. Defize ◽  
Marie-Jose Donath ◽  
Philippe Kastner ◽  
...  

2004 ◽  
Vol 286 (2) ◽  
pp. L249-L256 ◽  
Author(s):  
Ghenima Dirami ◽  
Gloria DeCarlo Massaro ◽  
Linda Biadasz Clerch ◽  
Una S. Ryan ◽  
Peter R. Reczek ◽  
...  

Retinoids play a key role in the formation of pulmonary alveoli. Lipid interstitial cells (LICs) of the alveolar wall store retinol and are concentrated at sites of alveolus formation, suggesting they are an endogenous source of retinoids for alveolus formation. We show in cultured rat lung cells that LICs synthesize and secrete all- trans retinoic acid (ATRA); its secretion is halved by dexamethasone, an inhibitor of alveolus formation. In a second alveolar wall cell, the pulmonary microvascular endothelial cell (PMVC), ATRA increases expression of the mRNA of cellular retinol binding protein-I (CRBP-I), a protein involved in ATRA synthesis. Serum-free, exogenous ATRA-free medium conditioned by LICs rich in retinol storage granules caused a 10-fold greater increase of CRBP-I mRNA in PMVCs than media conditioned by LICs with few retinol storage granules. This action of medium conditioned by retinol storage granule-rich LICs is decreased by a retinoic acid receptor pan-antagonist and by a retinoid X receptor pan-antagonist, suggesting the responsible molecule(s) is a retinoid and that retinoid signaling occurs in a paracrine fashion.


2013 ◽  
Vol 33 (16) ◽  
pp. 3343-3353 ◽  
Author(s):  
Prashanth Kumar Bajpe ◽  
Guus J. J. E. Heynen ◽  
Lorenza Mittempergher ◽  
Wipawadee Grernrum ◽  
Iris A. de Rink ◽  
...  

Retinoids play key roles in development, differentiation, and homeostasis through regulation of specific target genes by the retinoic acid receptor/retinoid X receptor (RAR/RXR) nuclear receptor complex. Corepressors and coactivators contribute to its transcriptional control by creating the appropriate chromatin environment, but the precise composition of these nuclear receptor complexes remains to be elucidated. Using an RNA interference-based genetic screen in mouse F9 cells, we identified the transcriptional corepressor CTBP2 (C-terminal binding protein 2) as a coactivator critically required for retinoic acid (RA)-induced transcription.CTBP2suppression by RNA interference confers resistance to RA-induced differentiation in diverse murine and human cells. Mechanistically, we find that CTBP2 associates with RAR/RXR at RA target gene promoters and is essential for their transactivation in response to RA. We show that CTBP2 is indispensable to create a chromatin environment conducive for RAR/RXR-mediated transcription by recruiting the histone acetyltransferase p300. Our data reveal an unexpected function of the corepressor CTBP2 as a coactivator for RAR/RXR in RA signaling.


2003 ◽  
Vol 23 (21) ◽  
pp. 7498-7509 ◽  
Author(s):  
Koichi Watashi ◽  
Makoto Hijikata ◽  
Ayako Tagawa ◽  
Takahiro Doi ◽  
Hiroyuki Marusawa ◽  
...  

ABSTRACT Hepatitis C virus (HCV) core protein (core) plays a significant role in the development of chronic liver diseases caused by HCV infection. We have discovered that the core sensitized all-trans-retinoic acid (ATRA)-induced cell death in MCF-7 cells. Activation of retinoic acid receptor alpha (RARα)-mediated transcription by the core was also seen in all the cell lines tested. By use of a yeast two-hybrid system, we identified Sp110b as a candidate for a core-interacting cellular factor. Although the function of Sp110b has remained unknown, we observed that Sp110b interacts with RARα and suppresses RARα-mediated transcription. These data suggest that Sp110b is a transcriptional cofactor negatively regulating RARα-mediated transcription. RNA interference-mediated reduction of endogenous Sp110b levels depressed the ability of the core to activate RARα-mediated transcription, suggesting an essential role for Sp110b in this pathway. The normal nuclear subcellular localization of Sp110b was altered by molecular interaction with the core to the cytoplasmic surface of the endoplasmic reticulum. This evidence suggests a model in which the core sequesters Sp110b from the nucleus and inactivates its corepressor function to activate RARα-mediated transcription. These findings likely describe a novel system in which a cytoplasmic viral protein regulates host cell transcription.


2006 ◽  
Vol 7 (3) ◽  
pp. 254
Author(s):  
F. Osaki ◽  
H. Takata ◽  
T. Suehiro ◽  
M. Inoue ◽  
K. Arii ◽  
...  

2002 ◽  
Vol 282 (3) ◽  
pp. L468-L476 ◽  
Author(s):  
Matthew Hind ◽  
Jonathan Corcoran ◽  
Malcolm Maden

Endogenous retinoids have been implicated in alveologenesis in both the rat and the mouse, and exogenous retinoic acid (RA) can reverse or partially reverse experimental emphysema in adult rat and mouse models by an unknown mechanism. In this study, we examine the cellular and molecular biology of retinoid signaling during alveologenesis in the mouse. We describe the temporal and spatial expression of the retinoid binding proteins CRBP-I, CRBP-II, and CRABP-I using RT-PCR and immunohistochemistry. We identify the retinoic acid receptor isoforms RAR-α1, RAR-β2, RAR-β4, and RAR-γ2 and describe their temporal and spatial expression using RT-PCR and in situ hybridization. We demonstrate that both retinoid binding proteins and RAR isoforms are temporally regulated and found within the alveolar septal regions during alveologenesis. These data support a role of dynamic endogenous RA signaling during alveolar formation.


1996 ◽  
Vol 24 (4) ◽  
pp. 566-572 ◽  
Author(s):  
A. J. Salerno ◽  
Z. He ◽  
A. Goos-Nilsson ◽  
H. Ahola ◽  
P. Mak

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