ATF6α is an endoplasmic reticulum (ER) transmembrane protein that senses misfolded proteins in the ER. During ER stress, ATF6α is proteolytically cleaved. The resulting N-terminal fragment is an active transcription factor, N-ATF6α, which induces genes that restore ER protein folding. N-ATF6α exerts potent, transient transcriptional activation of its target genes. This is due in part to its rapid degradation upon engagement in transcription. N-ATF6α transcriptional activation domain (TAD) and degradation domain (degron) map to the same N-terminal region, implying that both are linked. Mutations made in the TAD of N-ATF6α that decrease its activity also decrease its degradation, indicating that N-ATF6α degradation is coupled with its transcriptional activity. To elucidate how and why N-ATF6α degradation and activation are coupled, we examined the mechanism of N-ATF6α degradation, positing that ubiquitylation may target it for proteasome-mediated degradation. This study focused on delineating whether N-ATF6α is ubiquitylated, and if so, what domain(s) of N-ATF6α are ubiquitylated, and investigating the functional consequences of such ubiquitylation.