Unraveling the mechanism of a potent transcriptional activator

Zhen Lu, Steven P. Rowe, Brian B. Brennan, Sarah E. Davis, Renee E. Metzler, Johnathan J. Nau, Chinmay Y. Majmudar, Anna K. Mapp, Aseem Z. Ansari

Research output: Contribution to journalArticle

Abstract

Despite their enormous potential as novel research tools and therapeutic agents, artificial transcription factors (ATFs) that up-regulate transcription robustly in vivo remain elusive. In investigating an ATF that does function exceptionally well in vivo, we uncovered an unexpected relationship between transcription function and a binding interaction between the activation domain and an adjacent region of the DNA binding domain. Disruption of this interaction leads to complete loss of function in vivo, even though the activation domain is still able to bind to its target in the transcriptional machinery. We propose that this interaction parallels those between natural activation domains and their regulatory proteins, concealing the activation domain from solvent and the cellular milieu until it binds to its transcriptional machinery target. Inclusion of this property in the future design of ATFs should enhance their efficacy in vivo.

Original languageEnglish (US)
Pages (from-to)29689-29698
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number33
DOIs
StatePublished - Aug 19 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Lu, Z., Rowe, S. P., Brennan, B. B., Davis, S. E., Metzler, R. E., Nau, J. J., Majmudar, C. Y., Mapp, A. K., & Ansari, A. Z. (2005). Unraveling the mechanism of a potent transcriptional activator. Journal of Biological Chemistry, 280(33), 29689-29698. https://doi.org/10.1074/jbc.M504895200