Characterization of the activation domains of AP-2 family transcription factors.
Despite sequence variation, all AP-2 isotypes are capable of activating transcription, which indicates a functional conservation. We used this property to gain a unique insight into the structure and function of the activation 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 experiments indicate that similar sequence of amino acids in all AP-2 isotypes except Drosophila AP-2 alpha harbor their activation motifs. Within this sequence, fewer than 36 residues are critical for transcription activation. Our comparison studies and site-directed mutagenic analyses show that these critical amino acids are strategically placed within this sequence. These residues are interspersed with nonessential and influential residues that vary in composition and length, indicating a structural flexibility. The Drosophila AP-2 alpha has its partly conserved activation motif in an extended region about twice the length of other AP-2 isotypes. Our results reveal essential elements of the amino acid composition of activators in general and shed new light on the mechanism of transcription activation.
Wankhade
S
S
Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109, USA.
Yu
Y
Y
Weinberg
J
J
Tainsky
M A
MA
Kannan
P
P
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C493673:TFAP2A protein, human; C493674:TfAP-2 protein, Drosophila; D050656:Transcription Factor AP-2; D014157:Transcription Factors