Coregulator proteins

Like HATs, most functional HDACs are embedded in large multifunctional protein complexes, which also contain other chromatin modifying enzymes and coregulator proteins [1]. 

Another large family of coregulator proteins remodel chromatin, modify other transcription factots, and bridge the nuclear receptors to the basal ttanscription apparatus. 

Coregulator Protein Cell Content and Coactivators/Corepressors Ratio... 

In order for estrogen-mediated genomic activation to occur, the ligand-ER complex must bind to other nuclear proteins (coregulator proteins) that can either act as coactivators (stimulators of gene transcription) or corepressors (inhibitors of gene transcription) for access of the complex to the EREs (for... 

Since the discovery of this diverse family of coregulator proteins, a number of technologies has been utilized to address this need, such as FRET-based assays (Jeyakumar and Katzenellenbogen et al ... 

Figure 43-11. The hormone response transcription unit. The hormone response transcription unit is an assembly of DNA elements and bound proteins that interact, through protein-protein interactions, with a number of coactivator or corepressor molecules. An essential component is the hormone response element which binds the ligand (A)-bound receptor (R). Also Important are the accessory factor elements (AFEs) with bound transcription factors. More than two dozen of these accessory factors (AFs), which are often members of the nuclear receptor superfamily, have been linked to hormone effects on transcription. The AFs can interact with each other, with the liganded nuclear receptors, or with coregulators. These components communicate with the basal transcription complex through a coregulator complex that can consist of one or more members of the pi 60, corepressor, mediator-related, or CBP/p300 families (see Table 43-6).

Chromatin remodeling, transcription factor modification by various enzyme activities, and the communication between the nuclear receptors and the basal transcription apparatus are accomplished by protein-protein interactions with one or more of a class of coregulator molecules. The number of these coregulator molecules now exceeds 100, not counting species variations and splice variants. The first of these to be described was the CREB-binding protein, CBP. CBP, through an amino terminal domain, binds to phosphorylated serine 137 of CREB and mediates transactivation in response to cAMP. It thus is described as a coactivator. CBP and... 

The exact role of these coactivators is presendy under intensive investigation. Many of these proteins have intrinsic enzymatic activities. This is particularly interesting in view of the fact that acetylation, phosphorylation, methylation, and ubiquitination—as well as proteolysis and cellular translocation—have been proposed to alter the activity of some of these coregulators and their targets. 

The interaction of glucocorticoid receptors with GREs or other transcription factors is facilitated or inhibited by several families of proteins called steroid receptor coregulators, divided into coactivators and corepressors. The coregulators do this by serving as bridges between the receptors and other nuclear proteins and by expressing enzymatic activities such as histone acetylase or deacetylase, which alter the... 

Between 10% and 20% of expressed genes in a cell are regulated by glucocorticoids. The number and affinity of receptors for the hormone, the complement of transcription factors and coregulators, and post-transcription events determine the relative specificity of these hormones actions in various cells. The effects of glucocorticoids are mainly due to proteins synthesized from mRNA transcribed from their target genes. 

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