Minireview: nuclear receptor and coregulator proteomics--2012 and beyond

Abstract

The focus of our decade-long National Institutes of Health-sponsored NURSA Proteomics Atlas was to catalog and understand the composition of the steady-state interactome for all nuclear receptor coregulator complexes in a human cell. In this Perspective, we present a summary of the proteomics of coregulator complexes with examples of how one might use the NURSA data for future exploitation. The application of this information to the identification of the coregulator proteins that contribute to the molecular basis of polygenic diseases is emphasized.

Fig. 1.

Protein-protein interactions constitute the molecular backbone of cell biology, where select proteins assemble into meta-stable complexes to form bioactive units. The intrinsic tiered organization of the interactome can be represented in three discrete layers. These are 1) the obligatory MEMO complex modules; 2) the uniCORE isoforms; and 3) the transient CCI networks that likely represent the backbone of regulatory biology. Generally, interaction networks of transcriptional coregulators display two patterns: Type I CCI have stable multisubunit cores and highly preferential network partners, whereas Type II coregulators form multitudinous protein complex associations, as exemplified by the CCI network of estrogen receptor coactivator SRC-3 (NCOA3). IP, Immunoprecipitation; Pol II, polymerase II.