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Degradation Of Transcriptional Repressor Atf4 During Late-Phase Long-Term Potentiation, Spencer Smith
Degradation Of Transcriptional Repressor Atf4 During Late-Phase Long-Term Potentiation, Spencer Smith
Biology Theses
Maintenance of long-term synaptic plasticity requires gene expression mediated by cAMP-responsive element binding protein (CREB). Gene expression driven by CREB can commence only if the inhibition by a transcriptional repressor ATF4 (activating transcription factor 4; aka CREB2) is relieved. Previous research showed that the removal of ATF4 occurs through ubiquitin-proteasome-mediated proteolysis. Using chemically induced hippocampal long-term potentiation (cLTP) as a model system, we investigated the mechanisms that control ATF4 degradation. We observed that ATF4 phosphorylated at Serine-219 increases upon induction of cLTP and decreases by about 30 min thereafter. Proteasome inhibitor β-lactone prevents the decrease in ATF4. We found that …