Src kinase steroid receptor coactivator

The C terminal domain of SRC-1 contains two intrinsic transactivation domains: AD1 and AD2. The AD1 domain is required for the recruitment of secondary coactivators, such as cAMP response element binding protein (CREB)-binding protein (CBP) and the histone acetyltransferase p300 (Figure 1 ). Once SRC-1 has complexed with its ligand-bound receptor at the DNA, it must bring in additional proteins such as CBP and p300 to acetylate histone residues within the enhancer and promoter regions of the target gene so that transcription can successfully occur. In vitro transcription assays from chromatin-assembled templates have demonstrated that the interaction of p300 with the AD1 domain of SRC-1 is essential for SRC-1-mediated coactivation of ERα [ 32 ]. Furthermore, observations from the p300 protein structure have confirmed that it is the SRC-1 interacting domain and not the ERα-interacting domain, that is essential for p300-mediated coactivation of ERα [ 32 ]. Additional experiments have demonstrated that the C terminus of SRC-1 and also SRC-3 have intrinsic histone acetyltransferase activity (HAT); however, it remains unclear if such HAT activity is significant for target gene activation as the SRC-1 intrinsic HAT activity is much weaker than that in the CBP/p300 proteins [ 33 , 34 ]. SRC-1 also uses its AD1 domain to interact directly or indirectly via CBP/p300 with another HAT protein known as p/CAF (Figure 1 ). p/CAF primarily acetylates histone H3 and H4 to further facilitate chromatin remodeling at the site of NR target genes [ 35 ].

Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.

Src kinase steroid receptor coactivator

src kinase steroid receptor coactivator


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