il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

is achieved through its binding to the two classes of its intra-nuclear super receptors
(RAR and RXR) (Chambon 1996; Heyman et al. 1992; Mehta et al' 2003). Both RAR
and RXR receptors are the members of steroid-thyroid superhormone receptor family
which consists of more than 30 ligands such as estrogen, androgen, mineralocorticoid,
glucocorticoid, vitamin D3 and progesterone (Evans 1988; Green and Chambon 1988).
The RAR family of receptors are activated by binding to both all-trans RA (ATRA) and
9-cis RA, while RXR receptors bind only to 9-cis RA. However, a high concentrations of
RA are found to activate both RAR and RXR (Mangelsdorf et al. 1990). This may be
achieved through the direct binding of RA to the RXR receptors when the RAR receptor
binding sights are already saturated by high doses of the ligand or by the some unknown
pathway of intracellular conversion of RA to 9-cis RA'
IV.c.2.The structure of retinoic acid receptors: Each class of retinoid receptors
consists of three specific subtypes (c,Þ,y) (Napoli 1996). These subtypes consist of six
distinct domains referred to as A through F based on the homology amongst themselves
and other members of nuclear receptor subfamily (Mehta et al. 2003) (Fig.5). Each
retinoic acid receptor domain has a specific function'
There is a functional distinction between RXR and RAR receptors. As previously
mentioned RAR receptors are activated by all-trans retinoic acid and 9-cis retinoic acid
and are obligate heterodimeric partners of RXR receptors O{agy et al. 1998). However,
RXR receptors are found to be activated exclusively by 9-cis RA and they can act as both
homo and heterodimeric partners with other nuclear factors such as thyroid hormone
receptors, vitamin D3 receptors and peroxisome proliferator-activated receptors
(Chambon 1996;Mangelsdorf |ggL;Mangelsdorf andEvans 1995). Anumber of invitro
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