AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy
| Autor: | Elena Buerova, Kei Sakamoto, Christian Preisinger, Bernhard Lüscher, Jörg Vervoorts, Mareike Bütepage, Sarah Krieg, Stephan Geley, Dipanjan Chanda, Carolina M. Pfaff, Marc Dohmen, Georgios Agalaridis, Saifeldin N. Shehata, Xiaoqing Zhu, Jan Amelang, Elisabeth Pfeiffenberger, Dietbert Neumann |
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| Přispěvatelé: | Promovendi CD, Genetica & Celbiologie, Moleculaire Genetica, Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell General Physics and Astronomy A-769662 AMP-Activated Protein Kinases NUTRIENT Biochemistry ENERGY Mice REGULATE AUTOPHAGY 0302 clinical medicine Serine Autophagy-Related Protein-1 Homolog Phosphorylation lcsh:Science Cyclin Multidisciplinary Effector Chemistry Kinase Intracellular Signaling Peptides and Proteins Cyclin-Dependent Kinases Cell biology Multidisciplinary Sciences PHOSPHORYLATION SITES medicine.anatomical_structure Science & Technology - Other Topics Beclin-1 COMPUTATIONAL PLATFORM Science Protein Array Analysis CELLULAR AMPK Kinases Thiophenes General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Cyclins medicine Autophagy Animals Humans Protein kinase A Science & Technology IDENTIFICATION Biphenyl Compounds AMPK PATHWAYS General Chemistry PROTEIN-KINASE 030104 developmental biology Pyrones NIH 3T3 Cells lcsh:Q 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Nature Communications, 11(1):1032. Nature Publishing Group Dohmen, M, Krieg, S, Agalaridis, G, Zhu, X, Shehata, S N, Pfeiffenberger, E, Amelang, J, Bütepage, M, Buerova, E, Pfaff, C M, Chanda, D, Geley, S, Preisinger, C, Sakamoto, K, Lüscher, B, Neumann, D & Vervoorts, J 2020, ' AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy ', Nature Communications, vol. 11, no. 1, 1032 . https://doi.org/10.1038/s41467-020-14812-0 Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-14812-0 |
| Popis: | 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. AMPK integrates information about a cell’s energy status to inform decisions about cellular processes, including autophagy. Here the authors identify cyclin Y as an AMPK substrate, which phosphorylates cyclin Y and promotes its interaction with CDK16 to stimulate autophagy. |
| Databáze: | OpenAIRE |
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