The Survivin and cIAP1 anti-apoptotic proteins are differentially downregulated in response to endoplasmic reticulum stress

Authors:

Jay Brewster, Vicki Mercado

Mentor:

Jay Brewster, Associate Professor of Biology , Pepperdine University

The endoplasmic reticulum (ER) is an organelle tasked with synthesis and transport of 50% of new cellular proteins. Dysfunction within this organelle creates signals for repair, adaptation, and in severe cases, cellular apoptosis. Multiple human diseases have been associated with ER dysfunction, and the activation of apoptosis in important populations of cells. Inhibitor of Apoptosis (IAP) proteins are cytosolic proteins that play an anti-apoptotic role in the cytosol. The relationship between endoplasmic reticulum (ER) stress and the expression/stability of IAPs is not well characterized. The objective of this study was to characterize the affect of ER stress on the expression/stability of five members of the IAP family; XIAP, cIAP1, cIAP2, Survivin, and Livin. We also assessed how inhibition of the PI3kinase/Akt pathway affects expression of these proteins. In model cell lines (BHK21, A549), Survivin and cIAP1 expression was detected by immunoblot. ER stress was shown to induce a reduction of both Survivin and cIAP1 in a time and dose dependent manner, with Survivin displaying a more dynamic response. The phosphatidylinositol-3 kinase (PI3K) pathway has been associated with regulating expression of some IAP proteins. Inhibition of the PI3K decreased Survivin expression in both cell lines. It is known that ER stress up-regulates apoptosis. We have observed a decrease in the expression of anti-apoptotic proteins Survivin and cIAP1 in response to ER stress. However, the role that the decrease in anti-apoptotic proteins such as Survivin and cIAP1 has on the up-regulation of apoptosis should be further explored. Further research is also required to confirm the affects of ER stress upon regulation and stability of IAP expression.


Presented by:

Jay Brewster

Date:

Saturday, November 23, 2013

Time:

2:25 PM — 2:40 PM

Room:

Science 204

Presentation Type:

Oral Presentation

Discipline:

Biology