Objective: "NR-NET is a multidisciplinary consortium, whose activities are directed towards the understanding of the role of Nuclear Receptors (NRs) and coregulators
in metaflammatory disease.
in nuclear estrogen receptor action: from concept to therapeutic targeting.
2008; Zhu and Kyprianou 2008), amplification of the AR gene (Koivisto and Helin 1999), changes in the expression of AR coregulators
, and mutations of AR itself that enhance its transcriptional activity in response to the binding of ligands such as testosterones (Hull and Bostwick 2008).
can either enhance (coactivators) or reduce (corepressors) AR transactivation, resulting in altered transcription rates.
Breast cancer endocrine resistance: How growth factor signaling and estrogen receptor coregulators
Using a variety of techniques, researchers demonstrated they could rescue the cells by preventing certain members of a family of proteins called coregulators
from binding to the AF-2 domain.
Regulation of these actions is exerted by a number of different coregulators
including the coactivators DRIP and SRC, a less well known inhibitor, hairless, and beta-catenin.
Kinase-specific phosphorylation of the oestrogen receptor changes receptor interactions with ligand, deoxyribonucleic acid, and coregulators
associated with alterations in oestrogen and tamoxifen activity.
Aberrant activation of the androgen receptor (AR) can result from gene amplification, mutation, phosphorylation, activation of coregulators
, or androgen-independent activation.
Xenobiotic Receptor CoFactors and Coregulators
It is noteworthy that the diversity of transcriptional coregulators
mediating the effect of ERs on gene expression combined with variations in their expression levels and posttranslational modifications affect the specificity of the response depending on the cell type, ligand, or target gene considered (McDonnell and Wardell 2010).
O'Malley's landmark discoveries revealed the mechanism of hormone action and the critical importance of a previously undiscovered superfamily of mediators, the nuclear receptor coregulators