Nuclear receptor coactivators: master regulators of human health and disease

Abstract

Transcriptional coregulators (coactivators and corepressors) have emerged as the principal modulators of the functions of nuclear receptors and other transcription factors. During the decade since the discovery of steroid receptor coactivator-1 (SRC-1), the first authentic coregulator, more than 400 coregulators have been identified and characterized, and deciphering their function has contributed significantly to our understanding of their role in human physiology. Deregulated expression of coregulators has been implicated in diverse disease states and related pathologies. The advancement of molecular technologies has enabled us to better characterize the molecular associations of the SRC family of coactivators with other protein complexes in the context of gene regulation. These continuing discoveries not only expand our knowledge of the roles of coactivators in various human diseases but allow us to discover novel coactivator-targeting strategies for therapeutic intervention in these diseases.

Figure 1

Nuclear receptor coactivators control the physiology of multiple organs that are critical for various metabolic disorders and some rare genetic diseases as well. Target genes transcriptionally regulated by the coactivators are indicated in red.

Figure 2

Steroid receptor coactivators (SRC family members) are abundantly expressed and amplified in various forms of cancer.