NF-κB regulates protein quality control after heat stress through modulation of the BAG3-HspB8 complex
- PMID: 22302993
- DOI: 10.1242/jcs.091041
NF-κB regulates protein quality control after heat stress through modulation of the BAG3-HspB8 complex
Abstract
We previously found that the NF-κB transcription factor is activated during the recovery period after heat shock; moreover, we demonstrated that NF-κB is essential for cell survival after heat shock by activating autophagy, a mechanism that probably helps the cell to cope with hyperthermic stress through clearance of damaged proteins. In this study, we analyze the involvement of NF-κB in basal and heat-stress-induced protein quality control, by comparing the level of multiubiquitylated and/or aggregated proteins, and proteasome and autophagic activity in NF-κB-competent and NF-κB-incompetent cells. We show that NF-κB has only a minor role in basal protein quality control, where it modulates autophagosome maturation. By contrast, NF-κB is shown to be a key player in protein quality control after hyperthermia. Indeed, NF-κB-incompetent cells show highly increased levels of multiubiquitylated and/or aggregated proteins and aggresome clearance defects; a phenotype that disappears when NF-κB activity is restored to normal. We demonstrate that during heat shock recovery NF-κB activates selective removal of misfolded or aggregated proteins--a process also called 'aggrephagy'--by controlling the expression of BAG3 and HSPB8 and by modulating the level of the BAG3-HspB8 complex. Thus NF-κB-mediated increase in the level of the BAG3-HspB8 complex leads to upregulation of aggrephagy and clearance of irreversibly damaged proteins and might increase cell survival in conditions of hyperthermia.
Similar articles
-
HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency.FASEB J. 2018 Jul;32(7):3518-3535. doi: 10.1096/fj.201700558RR. Epub 2018 Feb 5. FASEB J. 2018. PMID: 29405094
-
A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis.PLoS Genet. 2015 Oct 23;11(10):e1005582. doi: 10.1371/journal.pgen.1005582. eCollection 2015 Oct. PLoS Genet. 2015. PMID: 26496431 Free PMC article.
-
Autophagy activation by NFkappaB is essential for cell survival after heat shock.Autophagy. 2009 Aug;5(6):766-83. doi: 10.4161/auto.8788. Epub 2009 Aug 20. Autophagy. 2009. PMID: 19502777
-
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.
-
Exploring the multifaceted roles of heat shock protein B8 (HSPB8) in diseases.Eur J Cell Biol. 2018 Apr;97(3):216-229. doi: 10.1016/j.ejcb.2018.03.003. Epub 2018 Mar 13. Eur J Cell Biol. 2018. PMID: 29555102 Review.
Cited by
-
NIK is required for NF-κB-mediated induction of BAG3 upon inhibition of constitutive protein degradation pathways.Cell Death Dis. 2015 Mar 12;6(3):e1692. doi: 10.1038/cddis.2014.584. Cell Death Dis. 2015. PMID: 25766331 Free PMC article.
-
A Crucial Role for the Protein Quality Control System in Motor Neuron Diseases.Front Aging Neurosci. 2020 Jul 21;12:191. doi: 10.3389/fnagi.2020.00191. eCollection 2020. Front Aging Neurosci. 2020. PMID: 32792938 Free PMC article.
-
_targeted Profiling of Heat Shock Proteome in Radioresistant Breast Cancer Cells.Chem Res Toxicol. 2019 Feb 18;32(2):326-332. doi: 10.1021/acs.chemrestox.8b00330. Epub 2019 Jan 11. Chem Res Toxicol. 2019. PMID: 30596229 Free PMC article.
-
NF-κB-Mediated Inflammation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Does Autophagy Play a Role?Int J Mol Sci. 2018 Apr 19;19(4):1245. doi: 10.3390/ijms19041245. Int J Mol Sci. 2018. PMID: 29671828 Free PMC article. Review.
-
BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implications for a proteasome-to-autophagy switch.Autophagy. 2014 Sep;10(9):1603-21. doi: 10.4161/auto.29409. Epub 2014 Jul 10. Autophagy. 2014. PMID: 25046115 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous