TY  - JOUR
A1  - Klimek, Christina
A1  - Jahnke, Ricarda
A1  - Wördehof, Judith
A1  - Kathage, Barbara
A1  - Stadel, Daniela
A1  - Behrends, Christian
A1  - Hergovich, Alexander
A1  - Höhfeld, Jörg
T1  - The Hippo network kinase STK38 contributes to protein homeostasis by inhibiting BAG3-mediated autophagy
T2  - Biochimica et biophysica acta. Molecular cell research
N2  - 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.
KW  - Autophagy
KW  - Proteostasis
KW  - Hippo signaling
KW  - Chaperone
KW  - Cytoskeleton
KW  - NDR1
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51515
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-515156
N1  - © 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/).
VL  - 1866
IS  - 10
SP  - 1556
EP  - 1566
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -