Title page for E-project-042605-010126

Project Type MQP

Submission date 2005-04-26

Author
Anthony J Hackett, BC

URN E-project-042605-010126

Sponsor Fumihiko Urano

Title An Engineered Receptor Coupled With a Small Molecule System Activates a Stress Signaling Pathway Critical to the ERAD Response

Advisor
Adams, David S., BB

Availability unrestricted

Abstract
Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded proteins in the ER. IRE1, an ER localized transmembrane protein kinase, is a sensor of unfolded proteins and plays an important role in regulating the cellular rescue response to ER stress. We have engineered FV2E-IRE1a, a drug controlled receptor that exploits the IRE1 cell rescue pathway. Addition of the drug AP20187 induces stress-uncoupled activation of FV2E IRE1 and causes IRE1 signaling. Our results indicate that the use of this system has utility in regulating the cytoprotective IRE1-ERAD pathway independently of other ER stress-induced signals, such as proapototic JNK signaling.

Files
MQPFinal.pdf

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Project Type	MQP
Submission date	2005-04-26
Author	Anthony J Hackett, BC
URN	E-project-042605-010126
Sponsor	Fumihiko Urano
Title	An Engineered Receptor Coupled With a Small Molecule System Activates a Stress Signaling Pathway Critical to the ERAD Response
Advisor	Adams, David S., BB
Availability	unrestricted
Abstract Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded proteins in the ER. IRE1, an ER localized transmembrane protein kinase, is a sensor of unfolded proteins and plays an important role in regulating the cellular rescue response to ER stress. We have engineered FV2E-IRE1a, a drug controlled receptor that exploits the IRE1 cell rescue pathway. Addition of the drug AP20187 induces stress-uncoupled activation of FV2E IRE1 and causes IRE1 signaling. Our results indicate that the use of this system has utility in regulating the cytoprotective IRE1-ERAD pathway independently of other ER stress-induced signals, such as proapototic JNK signaling.
Files	MQPFinal.pdf