Document Type

Post-Print

Publication Date

2013

Abstract

Direct and selective small molecule control of transcription factor activity is an appealing avenue for elucidating the cell biology mediated by transcriptional programs. However, pharmacologic tools to modulate transcription factor activity are scarce because transcription factors are not readily amenable to small molecule-mediated regulation. Moreover, existing genetic approaches to regulate transcription factors often lead to high nonphysiologic levels of transcriptional activation that significantly impair our ability to understand the functional implications of transcription factor activity. Herein, we demonstrate that small molecule-mediated conformational control of protein degradation is a generally applicable, chemical biological methodology to obtain small molecule-regulated transcription factors that modulate transcriptional responses at physiologic levels in human cells. Our establishment of this approach allows for the rapid development of genetically encoded, small molecule-regulated transcription factors to explore the biologic and therapeutic impact of physiologic levels of transcription factor activity in cells.

Document Object Identifier (DOI)

10.1021/ja402756

Publisher

American Chemical Society

Publication Information

Journal of the American Chemical Society

Included in

Chemistry Commons

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