Related Experiment Video

Updated: Jan 24, 2026

Identification of protein complexes with quantitative proteomics in S. cerevisiae
11:12

Identification of protein complexes with quantitative proteomics in S. cerevisiae

Published on: March 4, 2009

13.6K

Quantitative Interactome Proteomics Reveals a Molecular Basis for ATF6-Dependent Regulation of a Destabilized

Lars Plate1, Bibiana Rius2, Bianca Nguyen2

  • 1Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MB110, La Jolla, CA 92037, USA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.

Cell Chemical Biology
|May 21, 2019
PubMed

Insights

Activating the unfolded protein response (UPR) transcription factor ATF6 prevents toxic amyloid protein secretion by targeting it to ER proteostasis factors. This mechanism reduces amyloidogenic protein aggregation in systemic amyloid diseases.

Area of Science:

  • Cellular biology
  • Molecular medicine
  • Protein biochemistry

Background:

  • Systemic amyloid diseases involve toxic aggregation of amyloidogenic proteins.
  • Activation of the unfolded protein response (UPR) transcription factor ATF6 is a potential therapeutic strategy.
  • The precise mechanism by which ATF6 reduces amyloidogenic protein secretion is not well understood.

Purpose of the Study:

  • To elucidate the molecular mechanism by which ATF6 activation reduces the secretion of destabilized, amyloidogenic immunoglobulin light chains (LCs).
  • To investigate the role of ER proteostasis factors in ATF6-mediated reduction of LC secretion.

Main Methods:

  • Utilized a quantitative interactomics platform to analyze protein interactions.
  • Studied the effect of ATF6 activation on the targeting of destabilized LCs in the endoplasmic reticulum (ER).

Main Results:

  • ATF6 activation enhances the targeting of destabilized LCs to specific ER proteostasis factors.
  • This increased targeting retains amyloidogenic LCs within the ER, inhibiting their secretion.
  • Defined a molecular basis for ATF6-dependent reduction of destabilized LC secretion.

Conclusions:

  • ATF6 activation provides a mechanism to reduce the secretion of destabilized, amyloidogenic proteins.
  • Targeting ATF6 is a promising strategy for treating light-chain amyloidosis (AL) and related systemic amyloid diseases.
  • The findings highlight the importance of ER proteostasis in managing amyloidogenic protein disorders.
Keywords:
ATF6ER chaperonesER proteostasisER quality controlUnfolded Protein Response (UPR)XBP1squantitative proteomics

More Related Videos

JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics07:28

JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics

Published on: October 19, 2021

3.6K
Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics11:40

Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics

Published on: June 23, 2022

2.9K

Related Concept Videos

Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K
Regulated Protein Degradation02:58

Regulated Protein Degradation

3.1K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.9K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

2.0K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
19.7K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
3.5K