The retinoic acid receptor (RAR) is a type of
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...
which can also act as a ligand-activated transcription factor
that is activated by both
all-trans retinoic acid
Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth f ...
and
9-cis retinoic acid the retinoid active derivatives of Vitamin A .
They are typically found within the nucleus.
There are three retinoic acid receptors (RAR),
RAR-alpha,
RAR-beta, and
RAR-gamma, encoded by the , , genes, respectively. Within each RAR subtype there are various isoforms differing in their N-terminal region A.
Multiple splice variants have been identified in human RARs: four for , five for , and two for .
As with other
type II nuclear receptors, RAR heterodimerizes with
RXR and in the absence of ligand, the RAR/RXR dimer binds to hormone response elements known as retinoic acid response elements (RAREs) complexed with
corepressor In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, b ...
protein. Binding of agonist
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s to RAR results in dissociation of corepressor and recruitment of
coactivator
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA p ...
protein that, in turn, promotes
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
of the downstream target
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
into
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
and eventually
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
. In addition, the expression of RAR genes is under epigenetic regulation by promoter
methylation
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
.
Both the length and magnitude of the retinoid response is dependent of the degradation of RARs and RXRs through the
ubiquitin-proteasome.
This degradation can lead to elongation of the DNA transcription through disruption of the initiation complex or to end the response to facilitate further transcriptional programs.
Due to RAR/RXR heterodimers acting as subtrates to the non steroid hormone ligand retinoid they are extensively involved in cell differentiation, proliferation, and apoptosis.
See also
*
Retinoid receptor
Retinoid receptors are nuclear receptors (a class of protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, incl ...
*
Retinoid X receptor
The retinoid X receptor (RXR) is a type of nuclear receptor that is activated by 9-cis retinoic acid, which is discussed controversially to be of endogenous relevance, and 9-''cis''-13,14-dihydroretinoic acid, which is likely to be the major e ...
References
External links
*
Intracellular receptors
Transcription factors
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