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Comment
. 2019 Jul 18;26(7):909-910.
doi: 10.1016/j.chembiol.2019.07.003.

Interactome Changes Quantified to Identify the ER Proteostasis Network to Fight Amyloid Diseases

Ya-Juan Wang  1 , Ting-Wei Mu  2
Affiliations
Comment

Interactome Changes Quantified to Identify the ER Proteostasis Network to Fight Amyloid Diseases

Ya-Juan Wang et al. Cell Chem Biol. .

Abstract

In this issue of Cell Chemical Biology, Plate et al. (2019) used quantitative interactome proteomics to define the molecular mechanism by which ATF6 activation reduces amyloidogenic protein secretion. These results shed light on preventing the amyloid formation at the very early step to treat devastating amyloid diseases.

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Figures

Figure 1.
Figure 1.. An Overview of the Molecular Mechanism by which ATF6 Activation Reduces the Secretion of Destabilized ALLC
Under basal condition, ALLC, a destabilized amyloidogenic protein, is secreted into extracellular space and aggregates into toxic species. ATF6 activation retains ALLC in the ER by increasing its interactions with ATF6-dependent ER proteostasis factors, such as pro-folding chaperones, without apparent influence on its ER degradation. This substantially reduces the secretion of destabilized ALLC. XPB1s activation globally attenuates the interactions between ALLC and ER proteostasis network components and enhances the ER degradation of ALLC. This only modestly influences the secretion of ALLC.
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