Autoinhibition as a Transcriptional Regulatory Mechanism
- Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132; *Department of Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706; †Eleanor Roosevelt Institute, Denver, Colorado 80206; ‡Sloan-Kettering Memorial Cancer Center, New York, New York 10021
This extract was created in the absence of an abstract.
Excerpt
The modularity of transcription factors providesunique opportunities for biological regulation. Functionaldomains for DNA binding, activation, repression, andsubunit association are often delineated as discrete regions in both primary and tertiary protein structures. Inmany cases, these domains can function autonomously ina heterologous context. Furthermore, positive regulatorypathways, involving posttranslational modifications andprotein associations, often target a specific functional domain. Intramolecular interactions that negatively regulatea specific domain provide an additional level of control.This phenomenon, termed autoinhibition, is characterized by the observation that the deletion or mutation ofsequences outside of a domain can enhance the activity ofthat domain. Indeed, regions that negatively control theactivity of functional domains are frequently found intranscription factors within both prokaryotic and eukaryotic systems. Figure 1 schematically illustrates the role ofinhibitory sequences within the context of a generic transcription factor and lists some of the general and regulatory transcription factors in which autoinhibition regulates DNA binding, activation, or subunit configuration.This growing number of reports indicates that the autoinhibition phenomenon is widespread and represents an important regulatory strategy to modulate the activity oftranscription factors...
