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Journal ArticleDOI

Cloning of murine α and β retinoic acid receptors and a novel receptor γ predominantly expressed in skin

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TLDR
A novel RAR subtype is discovered whose expression in adult mouse seems to be highly restricted to skin, whereas RARα and RARβ are expressed in a variety of adult tissues, which suggests strongly that RAR α- and β-subtypes have different functions.
Abstract
In addition to having profound effects on embryonic pattern formation, retinoic acid (RA) has striking effects on differentiation and maintenance of epithelial cells in vivo and in vitro Skin is a major target organ for retinoids both in its normal and pathological states. The discovery of two human nuclear receptors for RA (hRAR alpha and hRAR beta) acting as transcriptional RA-inducible enhancer factors has provided a basis for understanding how RA controls gene expression. To investigate the specific role that RARs might play during development and in adult tissues, we have cloned the mouse RAR alpha and RAR beta (mRAR alpha and mRAR beta). Their amino-acid sequences are much more homologous to those of hRAR alpha and hRAR beta, respectively, than to each other, which suggests strongly that RAR alpha- and beta-subtypes have different functions. Most interestingly we have discovered a novel RAR subtype (mRAR gamma) whose expression in adult mouse seems to be highly restricted to skin, whereas RAR alpha and RAR beta are expressed in a variety of adult tissues. Furthermore, both mRAR alpha and mRAR gamma RNAs are readily detected in undifferentiated F9 embryocarcinoma (EC) cells, whereas mRAR beta messenger RNA is induced at least 30-fold in RA-differentiated F9 cells.

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Journal ArticleDOI

9-cis retinoic acid is a high affinity ligand for the retinoid X receptor

TL;DR: An experimental approach is reported that has identified 9-cis RA as an RXR ligand, up to 40-fold more potent than all-trans RA in transfection assays and binds with high affinity.
Journal ArticleDOI

Nuclear receptor that identifies a novel retinoic acid response pathway

TL;DR: By indicating the existence of an additional pathway through which retinoic acid may exert its effects, these data lead to a re-evaluation of retinoid physiology.
Journal ArticleDOI

The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus

TL;DR: It is reported that, in one APL-derived cell line, the RARα gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RARα fusion messenger RNA, which strongly implicate retinoic acid receptor α in leukaemogenesis.
Journal ArticleDOI

The PML-RARα fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR

TL;DR: In APL, the t(15;17) translocation generates an RAR mutant that could contribute to leukemogenesis through interference with promyelocytic differentiation, and this gene product contains a novel zinc finger motif common to several DNA-binding proteins.
Journal ArticleDOI

Characterization of three RXR genes that mediate the action of 9-cis retinoic acid.

TL;DR: Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA.
References
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Journal ArticleDOI

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Purification of Biologically Active Globin Messenger RNA by Chromatography on Oligothymidylic acid-Cellulose

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RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination.

TL;DR: RNA molecular weight measurements were carried out by gel electrophoresis under four different denaturing conditions including 99% formamide, 10 mM methyl mercury, 2.2 M formaldehyde, and 6 M urea at pH 3.8 to demonstrate reliable molecular weight determinations of denatured RNAs, especially those obtained by extrapolation.
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A human retinoic acid receptor which belongs to the family of nuclear receptors

TL;DR: The protein is homologous to the receptors for steroid hormones, thyroid hormones and vitamin D3, and appears to be a retinoic acid-inducible {Tans-acting enhancer factor, suggesting that the molecular mechanisms of the effect of vitamin A (vitamin A) on embryonic development, differentiation and tumour cell growth are similar to those described for other members of this nuclear receptor family.
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