Characterization of the activation domains of AP-2 family transcription factors

Despite sequence variation, all AP-2 isotypes are capable of activating tra nscription, which indicates a functional conservation. We used this propert y to gain a unique insight into the structure and function of the activatio n motifs of AP-2 family transcription factors. We have precisely localized the activation motif of human AP-2 alpha to amino acids 52-108. Our experim ents indicate that similar sequence of amino acids in all AP-2 isotypes exc ept Drosophila AP-2 alpha harbor their activation motifs, Within this seque nce, fewer than 36 residues are critical for transcription activation. Our comparison studies and site-directed mutagenic analyses show that these cri tical amino acids are strategically placed within this sequence. These resi dues are interspersed with nonessential and influential residues that vary in composition and length, indicating a structural flexibility. The Drosoph ila AP-2 alpha has its partly conserved activation motif in an extended reg ion about twice the length of other AP-2 isotypes. Our results reveal essen tial elements of the amino acid composition of activators in general and sh ed new light on the mechanism of transcription activation.