Prolonged-transcription factors

Prolonged-Transcription Factors The medication binds to the transcription factors on the DNA within the nucleus of the cell resulting in the transcription factor undergoing a physiological change. 

The effect of prolonged antioxidant therapy in relation to normal physiological processes (for example, redox cycling, cell-cell signalling, transcription factor activation) must be assessed. It is conceivable that the overload of one antioxidant by dietary supplementation (for example, a-tocopherol) may shift the levels of other antioxidants (for example, by decreasing ascorbate and /3-carotene concentrations), with unknown consequences. To assess the potential for lipid-soluble antioxidant treatment in inflammatory diseases such as RA, further investigations into these questions will be needed. 

Pennypacker K. R., Thai L., Hong J. S., and McMillian M. K. (1994). Prolonged expression of AP-1 transcription factors in the rat hippocampus after systemic kainate treatment. J. Neurosci. 14 3998-4006. 

Another important aspect of phosphorylation of transcription factors is the control of degradation. Phosphorylation of Jun by MAP kinase decreased ubiquitination, forestalling ubiquitin-dependent proteolysis, thus prolonging the lifetime of the transcription factor. This could prolong transcription, with obvious consequences. 

Figure 16.2. Signaling for memory formation. Short-term memory formation involves the activation of PKA, but no gene transcription. Activation of G-protein coupled receptors by excitatory stimuli activates adenylyl cyclase. This leads to the elevation of cAMP level, which subsequently activates PKA. Activated PKA undertakes modulation of channels thereby enhancing conductivity. However, prolonged/ repeated activation of this system results in nuclear translocation of PKA, which is the central molecular basis of long-term memory formation. Activated PKA and MAPK activate transcription factor CREB-1 while suppressing the inhibitory CREB-2. Activated CREB-1 binds to CRE region in promoters of early genes like C/EBP. Interestingly, C/EBP itself is a transcription factor that subsequently teams up with CREB to express late memory genes.

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