Assessing the permissiveness of transcriptional activator binding sites.
Both genetic and biochemical data suggest that transcriptional activators with little sequence homology nevertheless function through interaction with a shared group of coactivators. Here we show that a series of peptidomimetic transcriptional activation domains interact under cell-fiee and cellular conditions with the metazoan coactivator CBP despite differences in the positioning and identity of the constituent functional groups. Taken together, these results suggest that a key activator binding site within CBP is permissive, accepting multiple arrangements of hydrophobic functional groups. Further, this permissiveness is also observed with a coactivator from S. cerevisiae. Thus, the design of small molecule mimics of transcriptional activation domains with broad function may be more straightforward than previously envisioned.
Rowe
Steven P
SP
Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
Mapp
Anna K
AK
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D015534:Trans-Activators; D050882:CREB-Binding Protein