BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins
- PMID: 21252941
- PMCID: PMC3049430
- DOI: 10.1038/embor.2010.203
BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins
Abstract
Increasing evidence indicates the existence of selective autophagy pathways, but the manner in which substrates are recognized and targeted to the autophagy system is poorly understood. One strategy is transport of a particular substrate to the aggresome, a perinuclear compartment with high autophagic activity. In this paper, we identify a new cellular pathway that uses the specificity of heat-shock protein 70 (Hsp70) to misfolded proteins as the basis for aggresome-targeting and autophagic degradation. This pathway is regulated by the stress-induced co-chaperone Bcl-2-associated athanogene 3 (BAG3), which interacts with the microtubule-motor dynein and selectively directs Hsp70 substrates to the motor and thereby to the aggresome. Notably, aggresome-targeting by BAG3 is distinct from previously described mechanisms, as it does not depend on substrate ubiquitination.
Conflict of interest statement
The authors declare that they have no conflict of interest.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3049430/bin/embor2010203f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3049430/bin/embor2010203f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3049430/bin/embor2010203f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3049430/bin/embor2010203f4.gif)
Similar articles
-
PKM2 compensates for proteasome dysfunction by mediating the formation of the CHIP-HSP70-BAG3 complex and the aggregation of ubiquitinated proteins.FASEB J. 2022 Jan;36(1):e22121. doi: 10.1096/fj.202101342RR. FASEB J. 2022. PMID: 34951719
-
Breaking BAG: The Co-Chaperone BAG3 in Health and Disease.Trends Pharmacol Sci. 2016 Aug;37(8):672-688. doi: 10.1016/j.tips.2016.04.007. Epub 2016 May 6. Trends Pharmacol Sci. 2016. PMID: 27162137 Review.
-
Chaperone-mediated hierarchical control in targeting misfolded proteins to aggresomes.Mol Biol Cell. 2011 Sep;22(18):3277-88. doi: 10.1091/mbc.E11-05-0388. Epub 2011 Jul 20. Mol Biol Cell. 2011. PMID: 21775628 Free PMC article.
-
BAG3 and friends: co-chaperones in selective autophagy during aging and disease.Autophagy. 2011 Jul;7(7):795-8. doi: 10.4161/auto.7.7.15844. Autophagy. 2011. PMID: 21681022
-
HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy.Autophagy. 2008 Feb;4(2):237-9. doi: 10.4161/auto.5407. Epub 2007 Dec 11. Autophagy. 2008. PMID: 18094623 Review.
Cited by
-
The NDR family of kinases: essential regulators of aging.Front Mol Neurosci. 2024 May 13;17:1371086. doi: 10.3389/fnmol.2024.1371086. eCollection 2024. Front Mol Neurosci. 2024. PMID: 38803357 Free PMC article. Review.
-
BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.Cardiovasc Diabetol. 2024 Apr 25;23(1):140. doi: 10.1186/s12933-024-02216-z. Cardiovasc Diabetol. 2024. PMID: 38664681 Free PMC article.
-
CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly.PLoS Genet. 2024 Feb 5;20(2):e1011138. doi: 10.1371/journal.pgen.1011138. eCollection 2024 Feb. PLoS Genet. 2024. PMID: 38315730 Free PMC article.
-
BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates.Eur J Med Res. 2024 Feb 1;29(1):93. doi: 10.1186/s40001-024-01687-w. Eur J Med Res. 2024. PMID: 38297320 Free PMC article.
-
Dysregulated Autophagy and Sarcomere Dysfunction in Patients With Heart Failure With Co-Occurrence of P63A and P380S BAG3 Variants.J Am Heart Assoc. 2023 Dec 19;12(24):e029938. doi: 10.1161/JAHA.123.029938. Epub 2023 Dec 18. J Am Heart Assoc. 2023. PMID: 38108245 Free PMC article.
References
-
- Arndt V et al. (2010) Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol 20: 143–148 - PubMed
-
- Gamerdinger M, Clement AB, Behl C (2007) Cholesterol-like effects of selective cyclooxygenase inhibitors and fibrates on cellular membranes and amyloid-beta production. Mol Pharmacol 72: 141–151 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous