ACTIVATION FUNCTION-2 (AF-2) OF RETINOIC ACID RECEPTOR AND 9-CIS RETINOIC ACID RECEPTOR - PRESENCE OF A CONSERVED AUTONOMOUS CONSTITUTIVE ACTIVATING DOMAIN AND INFLUENCE OF THE NATURE OF THE RESPONSE ELEMENT ON AF-2 ACTIVITY

A motif essential for the transcriptional activation function 2 (AF-2) present in the E region of retinoic acid receptor (RAR) alpha and 9-c is retinoic acid receptor (RXR) alpha has been characterized as an amp hipathic alpha-helix whose main features are conserved between transcr iptionally active members of the nuclear receptor superfamily. This co nserved motif, which can activate autonomously in the absence of ligan d in animal and yeast cells, can be swapped between nuclear receptors without affecting the ligand dependency for activation of transcriptio n, thus indicating that a ligand-dependent conformational change is ne cessary to reveal the AF-2 activation potential within the E region of the nuclear receptor. Interestingly, we show that the precise nature of the direct repeat response element to which RAR/RXR heterodimers ar e bound can affect the activity of the AF-2s of the heterodimeric part ners, as well as the relative efficiency with which all-trans and 9-ci s retinoic acids activate the RAR partner.