SUMOylation of AMPK alpha 1 by PIAS4 specifically regulates mTORC1 signalling
| Autor: | Yan Yan, Tea Vallenius, Tomi P. Mäkelä, Iris P. L. Wong, Jorma J. Palvimo, Kari Vaahtomeri, Saara Ollila |
|---|---|
| Přispěvatelé: | Research Programs Unit, Tea Kaarina Vallenius / Principal Investigator, Mäkelä Lab, Faculty of Health Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cell biology
METFORMIN SUMO protein General Physics and Astronomy GROWTH-CONTROL mTORC1 AMP-Activated Protein Kinases Mechanistic Target of Rapamycin Complex 1 METABOLISM Article General Biochemistry Genetics and Molecular Biology UBIQUITIN LIGASE 03 medical and health sciences 0302 clinical medicine AMP-activated protein kinase Humans Poly-ADP-Ribose Binding Proteins Protein kinase A PHOSPHORYLATION 030304 developmental biology 0303 health sciences Multidisciplinary biology Activator (genetics) TOR Serine-Threonine Kinases ACTIVATED PROTEIN-KINASE Sumoylation AMPK BREAST-CANCER CELLS AMP KINASE LKB1-AMPK PATHWAY General Chemistry IN-VITRO Protein Inhibitors of Activated STAT Ubiquitin ligase Biological sciences Multiprotein Complexes 030220 oncology & carcinogenesis biology.protein 3111 Biomedicine Signal transduction Signal Transduction |
| Zdroj: | Nature Communications |
| Popis: | Article AMP-activated protein kinase (AMPK) inhibits several anabolic pathways such as fatty acid and protein synthesis, and identification of AMPK substrate specificity would be useful to understand its role in particular cellular processes and develop strategies to modulate AMPK activity in a substrate-specific manner. Here we show that SUMOylation of AMPKα1 attenuates AMPK activation specifically towards mTORC1 signalling. SUMOylation is also important for rapid inactivation of AMPK, to allow prompt restoration of mTORC1 signalling. PIAS4 and its SUMO E3 ligase activity are specifically required for the AMPKα1 SUMOylation and the inhibition of AMPKα1 activity towards mTORC1 signalling. The activity of a SUMOylation-deficient AMPKα1 mutant is higher than the wild type towards mTORC1 signalling when reconstituted in AMPKα-deficient cells. PIAS4 depletion reduced growth of breast cancer cells, specifically when combined with direct AMPK activator A769662, suggesting that inhibiting AMPKα1 SUMOylation can be explored to modulate AMPK activation and thereby suppress cancer cell growth. published version http://purl.org/eprint/status/PeerReviewed |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|