title: The problem of pyridinyl imidazole class inhibitors of MAPK14/p38α and MAPK11/p38β in autophagy research.
abstract: In addition to its established role in inflammation, the stress-activated p38 MAP kinase pathway plays major roles in the regulation of cell cycle, senescence, and autophagy. Robust studies could establish mechanistic links between MAPK11-MAPK14/p38 signaling and macroautophagy converging at ATG9-trafficking and BECN1 phosphorylation. However, several reports seem to monitor MAPK11-MAPK14/p38-dependence of autophagy exclusively by the use of the SB203580/SB202190 class of MAPK14/MAPK11/p38α/β inhibitors. In this "Letter to the editor" we present data to support our claim that these inhibitors interfere with autophagic flux in a MAPK11-MAPK14/p38-independent manner and hence should no longer be used as pharmacological tools in the analysis of MAPK11-MAPK14/p38-dependence of autophagy. We propose a general guideline from Autophagy with regard to this issue to avoid such misinterpretations in the future.
authors.affiliation: a Institute of Biochemistry; Medical School Hannover ; Hannover , Germany.
authors.forename: Manoj B
authors.initials: MB
authors.lastname: Menon
authors.forename: Sonam
authors.initials: S
authors.lastname: Dhamija
authors.forename: Alexey
authors.initials: A
authors.lastname: Kotlyarov
authors.forename: Matthias
authors.initials: M
authors.lastname: Gaestel
mesh_terms: D001343:Autophagy; D000071183:Autophagy-Related Proteins; D004791:Enzyme Inhibitors / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D019073:HT29 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007249:Inflammation / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D048290:Mitogen-Activated Protein Kinase 11 / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000737:chemistry*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C574794:ATG9A protein, human; D000071183:Autophagy-Related Proteins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008565:Membrane Proteins; D011725:Pyridines; D033921:Vesicular Transport Proteins; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
keywords: LC3; MAPK11-MAPK14/p38; SB202190; SB203580; SQSTM1; autophagy; vacuoles