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The Serpin Family pp 229–251Cite as

Endoplasmic Reticulum Stress and the Protein Overload Response in the Serpinopathies

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Abstract

The endoplasmic reticulum (ER) is an essential compartment for the synthesis and maturation of transmembrane and secretory proteins. Perturbations of protein folding by environmental or genetic factors result in the accumulation of misfolded proteins within the lumen of the ER. This leads to ER stress, a state defined as an imbalance between the rate of secretory protein synthesis and the capacity of the ER to fold new client proteins. The unfolded protein response (UPR) and the ER overload response (EOR) are two stress-induced signalling pathways emanating from the ER during the accumulation of either misfolded or well-folded client proteins, respectively. The serpins are unique as a class of proteins, since naturally occurring mutations appear to cause disease by triggering either the UPR or the EOR depending upon the specific nature of the mutation, such that different mutants of the same protein can preferentially trigger one or other response. Here, we discuss these signalling responses and how study of the serpinopathies has shed light on this area of cell biology.

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  1. Department of Medicine, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK

    Adriana Ordóñez PhD & Stefan J. Marciniak MD PhD

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Correspondence to Stefan J. Marciniak MD PhD .

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  1. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Margarethe Geiger

  2. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Felix Wahlmüller

  3. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Margareta Furtmüller

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Ordóñez, A., Marciniak, S.J. (2015). Endoplasmic Reticulum Stress and the Protein Overload Response in the Serpinopathies. In: Geiger, M., Wahlmüller, F., Furtmüller, M. (eds) The Serpin Family. Springer, Cham. https://doi.org/10.1007/978-3-319-22711-5_14

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