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Your search keyword '"Yu, Zhigang"' showing total 3 results
Start Over Author "Yu, Zhigang" Journal nature communications
3 results on '"Yu, Zhigang"'

1. Author Correction: Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor.

Author

Eftekharzadeh, Bahareh, Banduseela, Varuna C, Chiesa, Giulio, Martínez-Cristóbal, Paula, Rauch, Jennifer N, Nath, Samir R, Schwarz, Daniel MC, Shao, Hao, Marin-Argany, Marta, Di Sanza, Claudio, Giorgetti, Elisa, Yu, Zhigang, Pierattelli, Roberta, Felli, Isabella C, Brun-Heath, Isabelle, García, Jesús, Nebreda, Ángel R, Gestwicki, Jason E, Lieberman, Andrew P, and Salvatella, Xavier

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

2. Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor.

Author

Eftekharzadeh, Bahareh, Banduseela, Varuna C, Chiesa, Giulio, Martínez-Cristóbal, Paula, Rauch, Jennifer N, Nath, Samir R, Schwarz, Daniel MC, Shao, Hao, Marin-Argany, Marta, Di Sanza, Claudio, Giorgetti, Elisa, Yu, Zhigang, Pierattelli, Roberta, Felli, Isabella C, Brun-Heath, Isabelle, García, Jesús, Nebreda, Ángel R, Gestwicki, Jason E, Lieberman, Andrew P, and Salvatella, Xavier

Subjects
Animals, Mice, Transgenic, Humans, Mice, Receptors, Androgen, Androgens, Ligands, Nuclear Magnetic Resonance, Biomolecular, Solubility, Male, HSP70 Heat-Shock Proteins, HSP40 Heat-Shock Proteins, Protein Multimerization, Gene Knock-In Techniques, HEK293 Cells, Protein Aggregates, Protein Domains, Transgenic, Nuclear Magnetic Resonance, Biomolecular, Receptors, Androgen
Abstract

Molecular chaperones such as Hsp40 and Hsp70 hold the androgen receptor (AR) in an inactive conformation. They are released in the presence of androgens, enabling transactivation and causing the receptor to become aggregation-prone. Here we show that these molecular chaperones recognize a region of the AR N-terminal domain (NTD), including a FQNLF motif, that interacts with the AR ligand-binding domain (LBD) upon activation. This suggests that competition between molecular chaperones and the LBD for the FQNLF motif regulates AR activation. We also show that, while the free NTD oligomerizes, binding to Hsp70 increases its solubility. Stabilizing the NTD-Hsp70 interaction with small molecules reduces AR aggregation and promotes its degradation in cellular and mouse models of the neuromuscular disorder spinal bulbar muscular atrophy. These results help resolve the mechanisms by which molecular chaperones regulate the balance between AR aggregation, activation and quality control.

Published
2019

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