Southern California Conferences for Undergraduate Research

Southern California Conferences for Undergraduate Research

Moderate ER stress induces p44/p42 kinase activation and an ITPR-dependent apoptosis


Emily Lumley, Acadia Osborne, Amanda Scholl, Jessica Scott, Agustin Vargas


Jay Brewster, Professor of Biology, Pepperdine University

When unfolded proteins accumulate in the endoplasmic reticulum (ER), stress signaling pathways called the Unfolded Protein Response (UPR) are induced. Modeling of ER stress in cultured cells is often performed with high doses of poisons that arrest essential functions within the ER. In examining the potential implications of chronic ER stress signaling in organismal models, a modest ER stress would be anticipated as clinically appropriate. In this study, the ER was challenged with a 50-fold range of tunicamycin, an inhibitor of N-linked glycosylation. Tunicamycin induced cellular apoptosis and stress signaling over a range of concentration from 20 nM to 1000 nM. Activation of the ER transmembrane protein IRE1 was measured by quantification of IRE1-mediated splicing of the XBP1 pre-mRNA. IRE1 activity increased with dose of tunicamycin, but was detectably activated at doses as low as 20 nM. GRP78 expression, another marker of ER stress signaling, was increasingly induced with dosage of tunicamycin exposure. Interestingly, apoptosis induced by moderate levels of ER stress was susceptible to inhibitors of the inositol trisphosphate receptor (ITPR), a key release point for ER Ca2+ stores. This susceptibility was not observed with doses of tunicamycin above 40 nM, suggesting apoptosis induced by moderate doses is controlled by ITPR signaling. Assessment of cytosolic protein kinase pathways revealed the p44/p42 kinases to be specifically induced at tunicamycin concentrations from 20-40 nM while the p38 kinase was increasingly stimulated with increasing tunicamycin dose. This work collectively reveals moderate ER stress to generate a distinct stress signal relative to more severe ER stress exposure.

Presented by:

Amanda Scholl, Acadia Osborne


Saturday, November 17, 2012


9:15 AM — 9:30 AM


Bell Tower 1726

Presentation Type:

Oral Presentation