Transcriptional intermediary factor coactivator

Coactivators enhancing the transcriptional activity of steroid hormone receptors activators include SRC-1 (steroid-receptor co-activator 1) or TEF2 (transcriptional intermediary factor 2), which are recruited by the DNA/ steroid hormone receptor complex. Their main role is to attract other transcriptional coactivators with histone acetyltransferase activity in order to decondense chromatin and allow for the binding of components of the general transcription apparatus. 

Among the proteins that form part of the transcription machinery are found some cell factors that are produced in limited quantities. They are called cofactors of transcription (NCoA, for nuclear-receptor coactivator NCoI, for nuclear-receptor coinhibitor), formerly known as transcription intermediary factors (TIF) (McDonnell et al. 2002 McKenna et al. 1999). They constitute one of the classes of proteins that form part of the transcription machinery. These proteins are utilized by diverse types of intensifiers, that is to say, by sequences of DNA that anchor transcription factors, of which HRE are a particular case (Gruber et al. 2002 Mester et al. 1995). They do not interact directly with the DNA, but they do with the receptors and with the other elements of the transcription apparatus (Fig. 1.9). 

Gustafsson, J.A., Hubbard, R.E., Brzozowski, A.M. and Pike, A.C. (2002) Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor a. The Journal of Biological Chemistry, 277, 21862—21868. 

Of the protein kinases, protein kinase A is the best investigated and characterized (review Francis and Corbin, 1994). The functions of protein kinase A are diverse. Protein kinase A is involved in the regulation of metabolism of glycogen, lipids and sugars. Substrates of protein kinase A may be other protein kinases, as well as enzymes of intermediary metabolism. Protein kinase A is also involved in cAMP-stimulated transcription of genes that have a cAMP-responsive element in their control region (review Montminy, 1997). An increase in cAMP concentration leads to activation of protein kinase A which phosphorylates the transcription factor CREB at Ser 133. CREB only binds to the transcriptional coactivator CBP in the phosphorylated state and stimulates transcription (see Chapter 1.4.4.2). 

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