Education: Bachelor of Science in biology (May 2012)
McNair Project: Examining the Over-Expression of the Activating Transcription Factor 6 (2009)
Mentor: Andrew Beeser, Ph.D.
ATF6 is a transmembrane protein that resides in the Endoplasmic Reticulum (ER). When ER stress activates the Unfolded Protein Response (UPR), ATF6 is cleaved and transported into the nucleus. The UPR has been associated with many human diseases including cancer.
ATF6 is also involved with regulating the ER chaperones, which have been shown to restrict apoptosis, and has demonstrated a possible drug-resistance system by inducing cell survival. We questioned whether ATF6 could be an oncogene.
In addition to ATF6, we looked at the Her2 oncogene. Her2 is commonly up-regulated in breast cancer. The Her2 promoter contains an up-stream open reading frame (uORF) that inhibits the translation of the downstream Her2 gene. The UPR is implicated in the ability of uORF’s to repress down-stream genes. Since ATF6 is a key component of the UPR, we hypothesized that an increased expression of ATF6 would oppose the negative effect of the uORF and increase Her2 expression.