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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2014 (arch)     Display Documents

ID: 705662.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2014 (arch)
HSP70 Binding Protein HSPBP1 Regulates Chaperone Expression at a Posttranslational Level and is Essential for Spermatogenesis.
Authors:Rogon, Christian; Ulbricht, Anna; Hesse, Michael; Alberti, Simon; Vijayaraj, Preethi; Best, Diana; Adams, Ian R; Magin, Thomas M; Fleischmann, Bernd K; Höhfeld, Jörg
Date of Publication (YYYY-MM-DD):2014
Title of Journal:Molecular Biology of the Cell
Issue / Number:15
Start Page:2260
End Page:2271
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Molecular chaperones play key roles during growth, development, and stress survival. The ability to induce chaperone expression enables cells to cope with the accumulation of non-native proteins under stress, and to complete developmental processes with an increased requirement for chaperone assistance. Here we generate and analyse transgenic mice that lack the cochaperone HSPBP1, a nucleotide-exchange factor of HSP70 proteins and inhibitor of chaperone-assisted protein degradation. Male HSPBP1-/- mice are sterile because of impaired meiosis and massive apoptosis of spermatocytes. HSPBP1 deficiency in testes strongly reduces the expression of the inducible, anti-apoptotic HSP70 family members HSPA1L and HSPA2, the latter of which is essential for synaptonemal complex disassembly during meiosis. We demonstrate that HSPBP1 affects chaperone expression at a posttranslational level by inhibiting the ubiquitylation and proteasomal degradation of inducible HSP70 proteins. We further provide evidence that the cochaperone BAG2 contributes to HSP70 stabilization in tissues other than testes. Our findings reveal that chaperone expression is not only determined by regulated transcription but also by controlled degradation, with degradation-inhibiting cochaperones exerting essential prosurvival functions.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:thuem
Affiliations:MPI für molekulare Zellbiologie und Genetik
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