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 Transcriptional activators are critical factors in gene regulation, assisting in recruitment of coactivators and RNA polymerase II10.  Malfunction in transcriptional activators can lead to a variety of disease genotypes and phenotypes.  Construction of artificial transcriptional factors (ATF) has been used as a possibility to treat various diseases; cancer, heart disease, tumors, etc4

            The potency of an activator is dependent on the activation domain, a module that binds coactivators and assembles transcriptional machinery10.  Most activation domains are shielded from non-productive binding interactions and non-endogenous regulatory pathways.  Therefore, ATFs contain an additional binding domain that functions to harbor a hydrophobic ligand, and when binding of the original domain, it is thought that the ligands will undergo binding and stability alterations10

These ATFs have been used in re-activation of tumor suppressors, which are initially silenced through methylation of transcriptional promoters4.  This occurs with the construction of a specific ATF, which targeted the active sites with high affinity and selectivity.  It was found that the ATF constructed in this particular study was able to; induce apoptosis, knock down tumor cell invasion, and partially suppress breast cancer proliferation4.

The works of Kornberg detailing the transcriptional process contributed to the construction of the ATFs.  By better understanding the transcription mechanism, researchers have more knowledge to base the ATF construction on, and can target many diseases where the replication is faulty and correct the problem, as seen with the re-activation of a tumor suppressor.             

Kornberg's Contribution to Artificial Transcription Factors
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Click on the above asterik to listen to a discussion covering artificial transcriptional activators.