The Hippo network kinase STK38 contributes to protein homeostasis by inhibiting BAG3-mediated autophagy

  • Chaperone-assisted selective autophagy (CASA) initiated by the cochaperone Bcl2-associated athanogene 3 (BAG3) represents an important mechanism for the disposal of misfolded and damaged proteins in mammalian cells. Under mechanical stress, the cochaperone cooperates with the small heat shock protein HSPB8 and the cytoskeleton-associated protein SYNPO2 to degrade force-unfolded forms of the actin-crosslinking protein filamin. This is essential for muscle maintenance in flies, fish, mice and men. Here, we identify the serine/threonine protein kinase 38 (STK38), which is part of the Hippo signaling network, as a novel interactor of BAG3. STK38 was previously shown to facilitate cytoskeleton assembly and to promote mitophagy as well as starvation and detachment induced autophagy. Significantly, our study reveals that STK38 exerts an inhibitory activity on BAG3-mediated autophagy. Inhibition relies on a disruption of the functional interplay of BAG3 with HSPB8 and SYNPO2 upon binding of STK38 to the cochaperone. Of note, STK38 attenuates CASA independently of its kinase activity, whereas previously established regulatory functions of STK38 involve target phosphorylation. The ability to exert different modes of regulation on central protein homeostasis (proteostasis) machineries apparently allows STK38 to coordinate the execution of diverse macroautophagy pathways and to balance cytoskeleton assembly and degradation.
Metadaten
Author:Christina Klimek, Ricarda Jahnke, Judith Wördehof, Barbara Kathage, Daniela Stadel, Christian Behrends, Alexander Hergovich, Jörg Höhfeld
URN:urn:nbn:de:hebis:30:3-515156
DOI:https://doi.org/10.1016/j.bbamcr.2019.07.007
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31326538
Parent Title (English):Biochimica et biophysica acta. Molecular cell research
Publisher:Elsevier
Place of publication:Amsterdam [u. a.]
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/09/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/10/24
Tag:NDR1
Autophagy; Chaperone; Cytoskeleton; Hippo signaling; Proteostasis
Volume:1866
Issue:10
Page Number:11
First Page:1556
Last Page:1566
Note:
© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0