Ligand-dependent transactivation

In another recent example, Hashimoto reported photoaffinity experiments on retinoic acid receptors (RAR). Retinoic acid plays a critical role in cell proliferation and differentiation. RARs belong to the superfamily of nuclear/ thyroid hormone receptors. They consist of six transmembrane domains (A-F) which is a general feature of these receptors. The A/B domains have an autonomous transactivation function while the C-domain contains the Zn-finger, which binds to DNA. The large E-domain participates in ligand binding, dimerization, and ligand dependent transactivation. Finally, D- and F-domains help the orientation and stabilization of the E-domain. 

Lee Sk, Anzick SL, Choi JE, Bubendorf L, Guan XY, et al. 1999. A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptor in vivo. J. Biol. Chem. 274 34283-93... 

Mar, E., Delgado-Rodrigues, E., Nguyen, P., Baxter, J.D., Buehrer, B.M., Webb, P., Fletterick, R.J. and Guy, R.K. (2005) The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor. The Journal of Biological Chemistry, 280, 8060-8068. 

Barettino, D., M. D. M. Ruiz, and H. G. Stuimenberg. 1994. Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor. EMBO Journal 13 3039-3049. 

The LEDs of the ERa and the ER/1 share a similar overall architecture. Two separate transactivation domains (AF) mediate the transactivation of the ER an N-terminal hgand-independent activation fimction (AF-1) and a C-terminal ligand-dependent activation function (AF-2), which is located within the LED (Fig. 3). The surface of the AF-1 is composed of amino acids in helices 3,4, 5 and 12, and the binding of ligands alters the position of heHx... 

PHAM T A, HWUNG Y P, SANTISO M D, MCDONNELL D P and O MALLEY B W, Ligand-dependant and independent function of the transactivation regions of the human estrogen receptor in yeast , Mol Endocr 1992 6 1043-50. 

In addition to the G(Vy subunit mechanism, the opioid receptor could increase the Erkl/2 activity via a transactivation process. Using receptor mutants that have impeded calmodulin binding activity, Belvecha et al. [106] demonstrated the activation of Erkl/2 by the mu opioid receptor involved the calmodulin-dependent transactivation of the EGF receptor. Such mechanism represents the participation of metalloproteases in producing the ligand for EGF receptor as in the case of p>2-adrcncrgic receptor [107]. Whether this is occurring with the neuronal delta opioid receptor remains to be demonstrated. 

Dilworth FJ, Fromental-Ramain C, Rem-boutsika E, Benecke A, Chambon P. 1999. Ligand-dependent activation of transcription in vitro by retinoic acid receptor alpha and retinoid X receptor alpha heterodimers that mimics transactivation by retinoids in vivo. Proc. Natl. Acad. Sci. USA 96 1995-2000... 

Valentine, J.E., KaUdioven, E., White, R., Hoare, S., and Parker, M.G., Mutations in the estrogen receptor ligand binding domain discriminate between hormone-dependent transactivation and transrepression, J. Biol Chem., 275,25322-25329,2000. 

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