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BP: Fachverband Biologische Physik

BP 20: Regulation and Signaling

BP 20.7: Talk

Thursday, February 28, 2008, 11:30–11:45, C 243

Compartment Model for IRE1 Signalling of the Unfolded Protein Response — •Ronny Straube — Department of Systems Biology, Max-Planck-Institute for Dynamics of Complex Technical Systems, Sandtorstr. 1, 39106 Magdeburg, Germany

In recent years it became apparent that sustained stress in the endoplasmic reticulum (ER) is related to the emergence of several neurodegenerative diseases such as Alzheimer, Parkinson and ALS as well as diabetes and drug resistance of tumor cells. ER stress is caused by the accumulation of unfolded proteins in the secretory pathway. This leads to the activation of an extensive transcriptional response called Unfolded Protein Response (UPR) to restore ER homeostasis. UPR signalling occurs via 3 distinct and temporarily ordered pathways mediated by PERK, ATF6 and IRE1. As a result, proapoptotic and prosurvival signal molecules are activated simultaneously. So far it is unclear how the cell integrates this information to decide in favour of one or the other. However, recent experiments show that sustained signalling via the IRE1 pathway of the UPR promotes cell survival. Here, I propose the first model of the IRE1 signalling pathway which is based on the known molecular details of the interaction network and which shows good agreement with published experimental data.

[1] Lin et. al. (2007), Science 318, 944-949.