Targeting the transcriptional machinery with unique artificial transcriptional activators.
The link between a growing number of human diseases and misregulation of gene expression has spurred intense interest in artificial transcriptional activators that could be used to restore controlled expression of affected genes. To expand the repertoire of activation domains available for the construction of artificial transcriptional regulators, a selection strategy was used to identify two unique activation domain motifs. These activation domains bear little sequence homology to endogenous counterparts and bind to unique sites within the transcriptional machinery. A comparison with two well-characterized activation domains, VP2 and P201, demonstrated for the first time that functional potency is not solely dictated by binding affinity. Finally, the selection strategy described is readily applicable to the identification of small molecule activation domains.
Wu
Zhiqian
Z
Departments of Chemistry and Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Belanger
Garrette
G
Brennan
Brian B
BB
Lum
Jenifer K
JK
Minter
Aaron R
AR
Rowe
Steven P
SP
Plachetka
Annette
A
Majmudar
Chinmay Y
CY
Mapp
Anna K
AK
D000595:Amino Acid Sequence; D056892:Mediator Complex; D008969:Molecular Sequence Data; D019151:Peptide Library; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology
C058337:GAL11 protein, S cerevisiae; D056892:Mediator Complex; D019151:Peptide Library; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors