Review for "Mechanism of Hsp70 specialized interactions in protein translocation and the unfolded protein response"

2020 ◽  
Keyword(s):  
Unfolded Protein Response ◽  
Protein Translocation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Mechanism of Hsp70 specialized interactions in protein translocation and the unfolded protein response

Open Biology ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 200089
Author(s):  
Natacha Larburu ◽  
Christopher J. Adams ◽  
Chao-Sheng Chen ◽  
Piotr R. Nowak ◽  
Maruf M. U. Ali
Keyword(s):  
Unfolded Protein Response ◽  
Protein Translocation ◽  
Cellular Functions ◽  
Binding Partner ◽  
Unfolded Protein ◽  
Binding Partners ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Substrate Proteins ◽  
Partner Proteins

Hsp70 chaperones interact with substrate proteins in a coordinated fashion that is regulated by nucleotides and enhanced by assisting cochaperones. There are numerous homologues and isoforms of Hsp70 that participate in a wide variety of cellular functions. This diversity can facilitate adaption or specialization based on particular biological activity and location within the cell. In this review, we highlight two specialized binding partner proteins, Tim44 and IRE1, that interact with Hsp70 at the membrane in order to serve their respective roles in protein translocation and unfolded protein response signalling. Recent mechanistic data suggest analogy in the way the two Hsp70 homologues (BiP and mtHsp70) can bind and release from IRE1 and Tim44 upon substrate engagement. These shared mechanistic features may underlie how Hsp70 interacts with specialized binding partners and may extend our understanding of the mechanistic repertoire that Hsp70 chaperones possess.

scholarly journals Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response

2012 ◽  
Vol 442 (3) ◽  
pp. 639-648 ◽  
Author(s):  
Craig McKibbin ◽  
Alina Mares ◽  
Michela Piacenti ◽  
Helen Williams ◽  
Peristera Roboti ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Protein Translocation ◽  
Biological Processes ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Translocated Proteins ◽  
Protein Response

Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel mechanism that contributes to UPR activation.

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