Post-translational modification of activators

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DESCRIPTION (provided by applicant): It has recently been found that proteins of the ubiquitin/proteasome pathway are involved intimately in RNA polymerase II transcription. We demonstrated that the six proteasomal ATPases in concert with other factors, form a complex called APIS that is essential for efficient elongation. More recently, we have found that the APIS complex actively dissociates activator-DNA complexes in the presence of ATP, an activity that may be involved in the down-regulation of activator function. This discovery opens an interesting new area of transcription enzymology. It is particularly interesting in light of results presented here that suggest activator mono-ubiquitylation may be a critical event in regulating the potency of the APIS-mediated disassembly reaction. Identifying the mechanistic role(s) for activator ubiquitylation is emerging as a major issue intranscription enzymology. This project will focus on better understanding the negative regulation of Gal4-DNA interactions by the proteasomal ATPases (APIS complex). The effect of ubiquitylation and perhaps other post-translational modifications on this process will constitute a central part of these investigations. We anticipate that these studies will emerge as a paradigm for understanding an important new aspect of the activity of a large percentage of gene-specific transcription factors.