Murine RAR beta 4 displays reduced transactivation activity, lower affinity for retinoic acid, and no anti-AP1 activity

作者：Soprano DR; Scanlon E; Shukri M; Zhang ZP; Soprano KJ^*

来源：Journal of Cellular Biochemistry, 2000, 77(4): 604-614.

DOI：10.1002/(SICI)1097-4644(20000615)77:4<604::AID-JCB8>3.0.CO;2-T

• retinoic acid receptors
• isoforms
• retinoic acid
• anti-AP1
• ligand binding
• transactivation

The biological actions of retinoic acid (RA) are mediated by retinoic acid receptors (RAR alpha, beta, and gamma) and retinoid X receptors (RXR alpha, beta, and gamma). Each of the RARs is expressed as four to seven different isoforms. Four isoforms of RAR beta (beta 1, beta 2, beta 3, and beta 4), which differ only in their N-terminal sequence (A domain) have been described. These RAR beta isoforms display a specific pattern of expression in developing and adult animals and are highly evolutionarily conserved suggesting that they mediate distinct cellular effects of vitamin A. Experiments were performed to examine directly the RA-binding activity, transactivation activity, and anti-AP1 activity of each of these four RAR beta isoforms. The results demonstrate that RAR beta 1, beta 2, and beta 3 bind RA with a similar K-d value, have a similar EC50 value in RA-dependent transactivation assays and inhibit AP1 activity to a similar level. By contrast, RAR beta 4 has an Elevated K-d for RA, an increased EC50 value in RA-dependent transactivation assays and does not display the ability to inhibit AP1 activity. This provides additional evidence that at least one RAR isoform, RAR beta 4, may mediate distinct activities within a cell. Furthermore, these data suggest that the presence of an A domain in RAR beta is important for modulating these activities of RARs. J. Cell. Biochem. 77:604-614, 2000.

• 出版日期2000-4