Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1) is a
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 ...
that in humans is encoded by the ''RARA''
gene.
NR1B1 is a gene with a protein product and has a chromosomal location of 17q21.2. RARA codes for the nuclear hormone receptor Retinoic Acid Receptor, Alpha subtype, and are themselves transcription factors. There are another 2 subtypes of RARs, Beta subtype, and Gamma subtype.
Function
Retinoid
The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth.
Retinoids have many important functions throughout t ...
signaling is transduced by 2 families of nuclear receptors, retinoic acid receptor (
RAR RAR or Rar may refer to:
* Radio acoustic ranging, a non-visual technique for determining a ship's position at sea
* "rar", the ISO 639-2 code for the Cook Islands Māori language
* RAR (file format), a proprietary compressed archive file format in ...
) and retinoid X receptor (
RXR), which form RXR/RAR heterodimers. In the absence of ligand, DNA-bound
RXR/RARA represses transcription by recruiting the corepressors
NCOR1, SMRT (
NCOR2), and
histone deacetylase
Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...
. When ligand binds to the complex, it induces a conformational change allowing the recruitment of coactivators, histone acetyltransferases, and the basic transcription machinery.
Retinoic Acid Receptor Alpha, the protein, interacts with
retinoic acid, a derivative of
Vitamin A, which plays an important role in cell growth, differentiation, and the formation of organs in embryonic development.
Once Retinoic Acid binds to the RAR, they initiate
transcription and allow for their respective gene to be expressed.
Clinical significance
RA signaling has been correlated with several signaling pathways in early
embryonic development
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
. First, it participates in the formation of the
embryonic axis
Embryonic may refer to:
*Of or relating to an embryo
*Embryonic (album), ''Embryonic'' (album), a 2009 studio album by the Flaming Lips
*''Embryonics'', a 2005 album by Alchemist
{{Disambiguation ...
, which establishes symmetry in the offspring. RA also influences neural differentiation by regulating the expression of pro-neural induction factor Neurogenin 2 (
Neurog2). RA affects cardiogenesis, as it plays a role specifically in the formation of the
atrial chambers of the heart. RA also plays a role in the development of the pancreas, kidneys, lungs, and extremities.
that always involve rearrangement of the RARA gene are a cardinal feature of
acute promyelocytic leukemia
Acute promyelocytic leukemia (APML, APL) is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a ...
(APL; MIM 612376). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the
PML gene.
Interactions
Retinoic acid receptor alpha has been shown to
interact with:
*
BAG1,
*
CLOCK,
*
CCND3,
*
NCOA6,
*
NCOR1,
*
NCOR2,
*
NPAS2,
[
* NRIP1,]NR4A2
The nuclear receptor 4A2 (NR4A2) (nuclear receptor subfamily 4 group A member 2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the ''NR4A2'' gene. NR4A2 is a member of the nuclear receptor fam ...
,RXRA
Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 (nuclear receptor subfamily 2, group B, member 1) is a nuclear receptor that in humans is encoded by the ''RXRA'' gene.
Function
Retinoid X receptors (RXRs) and retinoic acid receptor ...
.
Genetic Studies
Knock-out mice studies showed that a deletion in one of the copies of the RARA gene did not create any observable defect, while deletion of both copies shows symptoms similar to that of Vitamin A deficiency. This proved that all 3 subtypes of RARs work redundantly.
Ligands
;Antagonists
* BMS-189453 (non selective)
* YCT529
YCT529 is a drug which acts as a potent and selective antagonist of the Vitamin A receptor retinoic acid receptor alpha (RAR-α). In studies on mice it produced a 99% reduction in sperm production, and it has proceeded to early stage human clini ...
(selective for RAR-α)
See also
* Retinoic acid receptor
* Retinoic X Receptor
* Acute promyelocytic leukemia
Acute promyelocytic leukemia (APML, APL) is a subtype of acute myeloid leukemia (AML), a cancer of the white blood cells. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease is characterized by a ...
References
Further reading
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{{DEFAULTSORT:Retinoic Acid Receptor Alpha
Intracellular receptors
Transcription factors