Transcription factor Phosphorylation

Fig. 1.32. Phosphorylation of the C-terminal domain of RNA polymerase II and the beginning of transcription. The transition from the initiation complex to actual begin of transcription is regulated via phosphorylation of the C-terminal domain (CTD) of RNA polymerase II. In the above model it is assumed that initially a complex is formed between TFIID and a holoenzyme of RNA polymerase consisting of RNA polymerase II and associated factors (mediators, SRB proteins) and the basal transcription factors. Phosphorylation of the C-terminal domain effects the dissociation of the RNA polymerase from the initation complex and the transition to the elongation phase. A protein kinase, which is part of TFIIH, is responsible for the phosphorylation. The nature of the signal that induces phosphorylation of RNA polymerase II remains unknown. SRB suppressor of RNA polymerase B. After Koleske and Young (1995).

Sheng, M., Thompson, M. A. and Greenberg, M. E., 1991, CREB a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases, Science, 252, pp 1427-30. 

Figure 21. Schematic of activation of the NF-xB transcription factor. Phosphorylation of the inhibitor protein IkB results in release of the sequestered NF-xB to the cytosol. NF-xB then translocates into the nucleus followed by phosphorylation and binds to the promoter region of the target gene. NF-xB transcription factor can regulate the transcription of either survival or pro-death genes See text for more detailed explanation.

Four mechanisms by which phosphorylation can modulate transcription-factor activity. The distinction between regulation of transcriptional activation by transcription-factor phosphorylation, and phosphorylation control of complex formation, is whether or not additional proteins are required to mediate the response. 

Which statement is NOT TRUE regarding the effect of transcription-factor phosphorylation on protein activity ... 

For example, STAT proteins are transcription factors phosphorylated by JAK-STAT receptors, and SMAD proteins are transcription factors phosphorylated by serine-threonine kinase receptors such as the transforming growth factor-(3(TGF- 3) receptor (see Chapter 11). 

One such hypotheses submits that most antidepressants enhance the expression of cyclo-AMP response element binding protein (CREB), which is a transcription factor that after phosphorylation binds to cyclo-AMP response elements localized in the promoter region of many genes including that coding for brain... 

Cell Cycle Control. Figure 1 Cell cycle regulation by Cyclin dependent kinases (CDKs). Different cyclins bound to different CDKs promote the transition from one cell cycle phase into another. CDK-dependent phosphorylation of Rb is required to release active E2F transcription factors, which promotes entry into S phase. 

CREB stands for cyclic-AMP response element (CRE) binding protein and is a transcription factor. When phosphorylated by cyclic AMP- and cyclic GMP-dependent Protein Kinases or other protein kinases it binds to gene promoters that contain a specific binding site. After binding, the respective transcription activity is modulated. 

Also, phosphorylation of Akt results in activation of sterol regulatory-element binding protein 1 (SREBP1), a key transcription factor involved in regulation of lipogenic enzymes. In addition, some of the effects of insulin on cell proliferation and survival may be explained by an Akt-dependent inhibition of apoptosis through phosphorylation and inactivation of proa-poptotic proteins (e.g., BAD, Caspase 9). 

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