title: S6K1 controls autophagosome maturation in autophagy induced by sulforaphane or serum deprivation.
abstract: It is well established that mTORC1 suppresses autophagy by phosphorylation and inactivation of proteins involved in autophagosome formation. However, the role of its substrate, p70S6 kinase1 (S6K1), in autophagy is quite controversial. In some models S6K1 activity correlates with autophagy suppression, however, some other studies show that S6K1 promotes rather than inhibits this process. Here, we investigated the role of S6K1 in prostate cancer cells (PC-3) and non-cancerous, mouse embryonic fibroblasts (MEF), either treated with autophagy inducer sulforaphane, an isothiocyanate derived from cruciferous plants, or deprived of serum. Our results indicate that constitutively active S6K1 decreases the level of LC3 processing and foci formation by autophagosomal vacuoles in cells treated with sulforaphane. On the other hand, presence of S6K1 is necessary for autophagosome maturation under conditions of autophagy induced by either sulforaphane or serum deprivation. Diminished level of S6K1 or lack of S6 kinases results in both, accumulation of autophagosomes and drop in the autophagolysosome number, and thus disturbs autophagy flux under stress conditions. Moreover, lack of S6 kinases reduces cell survival under stress conditions.
authors.affiliation: Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Hać
authors.affiliation: Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Domachowska
authors.affiliation: Laboratory of Electron Microscopy, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Narajczyk
authors.affiliation: Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Cyske
authors.affiliation: Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pawlik
authors.affiliation: Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland. Electronic address: anna.herman-antosiewicz@biol.ug.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Herman-Antosiewicz
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology; D019893:Ribosomal Protein S6 Kinases / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D016895:Culture Media, Serum-Free; D017879:Isothiocyanates; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D013454:Sulfoxides; D019893:Ribosomal Protein S6 Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; C016766:sulforaphane
keywords: Autophagy flux; LC3; MEF; PC-3; S6K1; S6K2; Sulforaphane