Coordinating Organismal Physiology Through the Unfolded Protein Response

Coordinating Organismal Physiology
R. Luke Wiseman & Cole M. Haynes
Release at: 2018
Pages: 218
First Edition
File Size: 5 MB
File Type: pdf
Language: English

Description of Coordinating Organismal Physiology Through the Unfolded Protein Response

The endoplasmic reticulum (ER) is a central stress-sensing platform responsible for regulating diverse biologic functions including protein secretion, lipid synthesis, and cellular metabolism. As such, genetic, environmental, and aging-related insults that challenge ER function (i.e., ER stress) can profoundly influence cellular physiology and contribute to the pathogenesis of diverse diseases. 

To protect cells against ER stress, eukaryotes evolved a complex, integrated stress-responsive signaling pathway called the Unfolded Protein Response (UPR). While initially identified in yeast as a single signaling pathway, the eukaryotic UPR is a complex signaling network consisting of three integrated signaling pathways activated downstream of the ER stress-sensing transmembrane proteins IRE1, PERK, and ATF6. 

In response to ER stress, these sensors are activated through diverse mechanisms, resulting in a transient attenuation of new protein synthesis and the activation of stress-responsive transcription factors such as XBP1s (activated downstream of IRE1), ATF4 (activated downstream of PERK), and ATF6 (the active transcription factor cleaved off of full-length ATF6). 

Through these mechanisms, the UPR functions to alleviate ER stress and adapt cellular physiology to protect against a given environmental, genetic, or aging-related insult. However, if activation of these pathways proves insufficient to alleviate a severe or chronic ER insult, the UPR promotes pro-apoptotic signaling to induce cell death. Through this combined adaptive and pro-apoptotic activity, the UPR has a critical role in both regulating cellular physiology and dictating cell fate in response to ER stress.

Content of Coordinating Organismal Physiology Through the Unfolded Protein Response

Adapting Secretory Proteostasis and Function Through the Unfolded
Protein Response  1
Madeline Y. Wong, Andrew S. DiChiara, Patrice H. Suen, Kenny Chen,
Ngoc-Duc Doan and Matthew D. Shoulders
Cell Non-autonomous UPRER Signaling . 27
Soudabeh Imanikia, Ming Sheng and Rebecca C. Taylor
The Unfolded Protein Response in the Immune Cell Development:
Putting the Caretaker in the Driving Seat  45
Simon J. Tavernier, Bart N. Lambrecht, and Sophie Janssens
Mitochondria-Associated Membranes and ER Stress  73
Alexander R. van Vliet and Patrizia Agostinis
Coordinating Organismal Metabolism During Protein Misfolding in
the ER Through the Unfolded Protein Response  103
Vishwanatha K. Chandrahas, Jaeseok Han and Randal J. Kaufman
ER Stress and Neurodegenerative Disease: A Cause or Effect
Relationship?  131
Felipe Cabral-Miranda and Claudio Hetz
Driving Cancer Tumorigenesis and Metastasis Through UPR
Signaling  159
Alexandra Papaioannou and Eric Chevet
ER Protein Quality Control and the Unfolded Protein Response
in the Heart. 193
A. Arrieta, E.A. Blackwood, and C.C. Glembotski

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