• PMID: 24899640
• Gene Name: BAG2
• Condition: Essential for spermatogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Associated genes: HSPBP1, BAG2, HSPA4
• Other associated phenotypes: Essential for spermatogenesis

HSP70-binding protein HSPBP1 regulates chaperone expression at a posttranslational level and is essential for spermatogenesis

Rogon C, Ulbricht A, Hesse M, Alberti S, Vijayaraj P, Best D, Adams IR, Magin TM, Fleischmann BK, Höhfeld J.

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 nonnative proteins under stress and complete developmental processes with an increased requirement for chaperone assistance. Here we generate and analyze 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, antiapoptotic 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 determined not only by regulated transcription, but also by controlled degradation, with degradation-inhibiting cochaperones exerting essential prosurvival functions. CI - © 2014 Rogon, Ulbricht, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). FAU - Rogon, Christian AU - Rogon C AD - Institut für Zellbiologie and Bonner Forum Biomedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53121 Bonn, Germany. FAU - Ulbricht, Anna AU - Ulbricht A AD - Institut für Zellbiologie and Bonner Forum Biomedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53121 Bonn, Germany. FAU - Hesse, Michael AU - Hesse M AD - Institut für Physiologie I, Life and Brain Centre, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53105 Bonn, Germany. FAU - Alberti, Simon AU - Alberti S AD - Institut für Zellbiologie and Bonner Forum Biomedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53121 Bonn, Germany. FAU - Vijayaraj, Preethi AU - Vijayaraj P AD - Abteilung für Zellbiochemie, Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53115 Bonn, Germany. FAU - Best, Diana AU - Best D AD - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. FAU - Adams, Ian R AU - Adams IR AD - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom. FAU - Magin, Thomas M AU - Magin TM AD - Abteilung für Zellbiochemie, Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53115 Bonn, Germany. FAU - Fleischmann, Bernd K AU - Fleischmann BK AD - Institut für Physiologie I, Life and Brain Centre, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53105 Bonn, Germany.