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Int. J. Mol. Sci. 2017, 18(1), 69; doi:10.3390/ijms18010069

BAG2 Interferes with CHIP-Mediated Ubiquitination of HSP72

Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, D-55099 Mainz, Germany
Present address: Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
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Author to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Received: 29 November 2016 / Revised: 23 December 2016 / Accepted: 27 December 2016 / Published: 30 December 2016
(This article belongs to the Special Issue Neuronal Protein Homeostasis in Health and Disease)
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Abstract

The maintenance of cellular proteostasis is dependent on molecular chaperones and protein degradation pathways. Chaperones facilitate protein folding, maturation, and degradation, and the particular fate of a misfolded protein is determined by the interaction of chaperones with co-chaperones. The co-factor CHIP (C-terminus of HSP70-inteacting protein, STUB1) ubiquitinates chaperone substrates and directs proteins to the cellular degradation systems. The activity of CHIP is regulated by two co-chaperones, BAG2 and HSPBP1, which are potent inhibitors of the E3 ubiquitin ligase activity. Here, we examined the functional correlation of HSP72, CHIP, and BAG2, employing human primary fibroblasts. We showed that HSP72 is a substrate of CHIP and that BAG2 efficiently prevented the ubiquitination of HSP72 in young cells as well as aged cells. Aging is associated with a decline in proteostasis and we observed increased protein levels of CHIP as well as BAG2 in senescent cells. Interestingly, the ubiquitination of HSP72 was strongly reduced during aging, which revealed that BAG2 functionally counteracted the increased levels of CHIP. Interestingly, HSPBP1 protein levels were down-regulated during aging. The data presented here demonstrates that the co-chaperone BAG2 influences HSP72 protein levels and is an important modulator of the ubiquitination activity of CHIP in young as well as aged cells. View Full-Text
Keywords: aging; BAG2; CHIP; HSP72; proteostasis; ubiquitination aging; BAG2; CHIP; HSP72; proteostasis; ubiquitination
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Schönbühler, B.; Schmitt, V.; Huesmann, H.; Kern, A.; Gamerdinger, M.; Behl, C. BAG2 Interferes with CHIP-Mediated Ubiquitination of HSP72. Int. J. Mol. Sci. 2017, 18, 69.

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