The homeostatic regulation of the unfolded protein response

29 Apr 2011

Hana El-Samad
Departments of Biochemistry and Biophysics
Univeristy of California, San Francisco,
and the California Institute for Quantitative Biosciences


The unfolded protein response (UPR) is an intracellular signaling pathway that maintains proper function of the endoplasmic reticulum (ER), counteracting variable stresses that impair folding of proteins. In this capacity, the UPR is at the center of many normal physiological responses and pathologies. In this study, we quantitatively interrogate the homeostatic capacity of the UPR. Moving between a predictive computational model and quantitative dynamic measurements, we establish how the dynamic behavior of the UPR is fine tuned, especially with regard to important performance criteria such as sensitivity and shutoff kinetics. In this quest, we describe new computational approaches that allow for the rigorous analysis of underdetermined models of biological dynamics.

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