2. Academic Validation
  3. AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy

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

  • Nat Commun. 2020 Feb 25;11(1):1032. doi: 10.1038/s41467-020-14812-0.
Marc Dohmen # 1 2,  Sarah Krieg # 1,  Georgios Agalaridis 1 3,  Xiaoqing Zhu 4,  Saifeldin N Shehata 5,  Elisabeth Pfeiffenberger 6,  Jan Amelang 1,  Mareike Bütepage 1,  Elena Buerova 1,  Carolina M Pfaff 1 7,  Dipanjan Chanda 4,  Stephan Geley 6,  Christian Preisinger 8,  Kei Sakamoto 5 9,  Bernhard Lüscher 10,  Dietbert Neumann 11 12,  Jörg Vervoorts 13
Affiliations

Affiliations

  • 1 Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52074, Aachen, Germany.
  • 2 Center for Translational & Clinical Research Aachen (CTC-A), Medical School, RWTH Aachen University, 52074, Aachen, Germany.
  • 3 Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429, Bergisch Gladbach, Germany.
  • 4 CARIM School for Cardiovascular Diseases, Maastricht University, P.O. box 616, 6200 MD, Maastricht, The Netherlands.
  • 5 Nestlé Research, EPFL Innovation Park, 1015, Lausanne, Switzerland.
  • 6 Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innrain 80/82, 6020, Innsbruck, Austria.
  • 7 AstraZeneca GmbH, Tinsdaler Weg 183, 22880, Wedel, Germany.
  • 8 Proteomics Facility, Interdisciplinary Center for Clinical Research (IZKF) Aachen, Medical School, RWTH Aachen University, 52074, Aachen, Germany.
  • 9 Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
  • 10 Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52074, Aachen, Germany. [email protected].
  • 11 CARIM School for Cardiovascular Diseases, Maastricht University, P.O. box 616, 6200 MD, Maastricht, The Netherlands. [email protected].
  • 12 Department of Pathology, University Medical Center Maastricht, 6229 HX, Maastricht, The Netherlands. [email protected].
  • 13 Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52074, Aachen, Germany. [email protected].
  • # Contributed equally.
PMID: 32098961 DOI: 10.1038/s41467-020-14812-0
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.

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