title: Microtubules depolymerization caused by the CK1 inhibitor IC261 may be not mediated by CK1 blockage.
abstract: The ubiquitously expressed serine/threonine specific casein kinase 1 (CK1) family plays important roles in the regulation of various physiological processes. Small-molecule inhibitors, such as the CK1δ/ε selectively inhibitor IC261, have been used to antagonize CK1 phosphorylation events in cells in many studies. Here we present data to show that, similarly to the microtubule destabilizing agent nocodazole, IC261 depolymerizes microtubules in interphase cells. IC261 treatment of interphase cells affects the morphology of the TGN and Golgi apparatus as well as the localization of CK1δ, which co-localizes with COPI positive membranes. IC261-induced depolymerization of microtubules is rapid, reversible and can be antagonized by pre-treatment of cells with taxol. At lower concentrations of IC261, mitotic spindle microtubule dynamics are affected; this leads to cell cycle arrest and, depending on the cellular background, to apoptosis in a dose-dependent manner. In addition, FACS analysis revealed that IC261 could induce apoptosis independent of cell cycle arrest. In summary this study provides additional and valuable information about various IC261-induced effects that could be caused by microtubule depolymerization rather than by inhibition of CK1. Data from studies that have used IC261 as an inhibitor of CK1 should be interpreted in light of these observations.
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stöter
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Krüger
authors.affiliation: School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Banting
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knippschild
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D047389:Casein Kinase I / Q000037:antagonists & inhibitors*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007399:Interphase; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; C411652:IC 261; D007211:Indoles; D050257:Tubulin Modulators; D010696:Phloroglucinol; D047389:Casein Kinase I