Autor: |
Sarah J. Backe, Rebecca A. Sager, Jennifer A. Heritz, Laura A. Wengert, Katherine A. Meluni, Xavier Aran-Guiu, Barry Panaretou, Mark R. Woodford, Chrisostomos Prodromou, Dimitra Bourboulia, Mehdi Mollapour |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Cell Reports, Vol 42, Iss 7, Pp 112807- (2023) |
Druh dokumentu: |
article |
ISSN: |
2211-1247 |
DOI: |
10.1016/j.celrep.2023.112807 |
Popis: |
Summary: Cellular homeostasis relies on both the chaperoning of proteins and the intracellular degradation system that delivers cytoplasmic constituents to the lysosome, a process known as autophagy. The crosstalk between these processes and their underlying regulatory mechanisms is poorly understood. Here, we show that the molecular chaperone heat shock protein 90 (Hsp90) forms a complex with the autophagy-initiating kinase Atg1 (yeast)/Ulk1 (mammalian), which suppresses its kinase activity. Conversely, environmental cues lead to Atg1/Ulk1-mediated phosphorylation of a conserved serine in the amino domain of Hsp90, inhibiting its ATPase activity and altering the chaperone dynamics. These events impact a conformotypic peptide adjacent to the activation and catalytic loop of Atg1/Ulk1. Finally, Atg1/Ulk1-mediated phosphorylation of Hsp90 leads to dissociation of the Hsp90:Atg1/Ulk1 complex and activation of Atg1/Ulk1, which is essential for initiation of autophagy. Our work indicates a reciprocal regulatory mechanism between the chaperone Hsp90 and the autophagy kinase Atg1/Ulk1 and consequent maintenance of cellular proteostasis. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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