AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

Marc Dohmen, Sarah Krieg, Georgios Agalaridis, Xiaoqing Zhu, Saifeldin N. Shehata, Elisabeth Pfeiffenberger, Jan Amelang, Mareike Buetepage, Elena Buerova, Carolina M. Pfaff, Dipanjan Chanda, Stephan Geley, Christian Preisinger, Kei Sakamoto, Bernhard Lüscher*, Dietbert Neumann*, Joerg Vervoorts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. Using protein microarrays, we identify Cyclin Y as an AMPK substrate that is phosphorylated at Serine 326 (S326) both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the Cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.

Original languageEnglish
Article number1032
Number of pages18
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 25 Feb 2020

Keywords

  • PROTEIN-KINASE
  • COMPUTATIONAL PLATFORM
  • PHOSPHORYLATION SITES
  • REGULATE AUTOPHAGY
  • CELLULAR AMPK
  • ENERGY
  • PATHWAYS
  • NUTRIENT
  • IDENTIFICATION
  • A-769662

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