Journal article

DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy

Pietri Puustinen, Anne Keldsbo, Elisabeth Corcelle-Termeau, Kevin Ngoei, Stine L Sonder, Thomas Farkas, Klaus Kaae Andersen, Jon S Oakhill, Marja Jaattela

AUTOPHAGY | TAYLOR & FRANCIS INC | Published : 2020

Abstract

Macroautophagy/autophagy is a central component of the cytoprotective cellular stress response. To enlighten stress-induced autophagy signaling, we screened a human kinome siRNA library for regulators of autophagic flux in MCF7 human breast carcinoma cells and identified the catalytic subunit of DNA-dependent protein kinase PRKDC/DNA-PKcs as a positive regulator of basal and DNA damage-induced autophagy. Analysis of autophagy-regulating signaling cascades placed PRKDC upstream of the AMP-dependent protein kinase (AMPK) complex and ULK1 kinase. In normal culture conditions, PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and ..

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Grants

Awarded by Danish National Research Foundation


Awarded by European Research Council


Awarded by Danish Cancer Society


Awarded by Danish Council for Independent Research


Awarded by Novo Nordisk Foundation


Awarded by TRANSAUTOPHAGY COST Action


Funding Acknowledgements

M.J. was supported by the Danish National Research Foundation (DNRF125), European Research Council (AdG 340751), Danish Cancer Society (R40-A1793 and R167-A11061), Danish Council for Independent Research (0602-02707B) and Novo Nordisk Foundation (12OC0001341). J.S.O was supported by grants from the National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC), and in part by the Victorian Government's Operational Infrastructure Support Program. We would also like to acknowledge the support of the TRANSAUTOPHAGY COST Action (CA15138).