Autoinhibitory Domains: Modular Effectors of Cellular Regulation

Annual Review of Cell and Developmental Biology

Vol. 18:421-462 (Volume publication date November 2002)
First published online as a Review in Advance on June 28, 2002
https://doi.org/10.1146/annurev.cellbio.18.031502.133614

Abstract

AbstractAutoinhibitory domains are regions of proteins that negatively regulate the function of other domains via intramolecular interactions. Autoinhibition is a potent regulatory mechanism that provides tight “on-site” repression. The discovery of autoinhibition generates valuable clues to how a protein is regulated within a biological context. Mechanisms that counteract the autoinhibition, including proteolysis, post-translational modifications, as well as addition of proteins or small molecules in trans, often represent central regulatory pathways. In this review, we document the diversity of instances in which autoinhibition acts in cell regulation. Seven well-characterized examples (e.g., σ70, Ets-1, ERM, SNARE and WASP proteins, SREBP, Src) are covered in detail. Over thirty additional examples are listed. We present experimental approaches to characterize autoinhibitory domains and discuss the implications of this widespread phenomenon for biological regulation in both the normal and diseased states.

Keywords