Autoinhibition as a Transcriptional Regulatory Mechanism

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...