title: New potential peptide therapeutics perturbing CK1δ/α-tubulin interaction.
abstract: Members of the CK1 family are highly conserved serine/threonine specific kinases being expressed in all eukaryotes. They are involved in many cellular processes and therefore tightly regulated. A central mechanism to modulate CK1 activity is via interaction with cellular proteins. CK1δ interacts with α-/β-tubulin and is involved in the regulation of microtubule dynamics. Therefore, it is important to identify the structural elements responsible for the interaction between these proteins. Using a peptide library covering the human CK1δ amino acid sequence in SPR and ELISA analyses, we identified peptide 39 (P39), encompassing aa361-aa375 of CK1δ, as a prominent binding partner of α-tubulin. P39 decreases α-tubulin phosphorylation by CK1δ and reduces the thermodynamic stability of α-tubulin in fluorescence thermal shift assays. Furthermore, P39 induces an inhibition of mitotic progression and a disruption of cells entering mitosis in CV-1 cells. Taken together our data provide valuable information regarding the interaction of CK1δ and α-tubulin and a novel approach for the development of pharmacological tools to inhibit proliferation of cancer cells.
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Krüger
authors.affiliation: Interfaculty Institute of Biochemistry, Tübingen University, Hoppe-Seyler-Straße 4, 72076 Tübingen, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.affiliation: European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors.forename: Panagiotis L
authors.initials: PL
authors.lastname: Kastritis
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Bischof
authors.affiliation: Institute for Pharmacology and Toxicology, Ulm University Hospital, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Barth
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.affiliation: Faculty of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15701 Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Vorgias
authors.affiliation: Department of Biomedical Sciences, and CNR Institute of Neurosciences, University of Padua, Via Ugo Bassi 58/B, 35121 Padova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sarno
authors.affiliation: Department of Biomedical Sciences, and CNR Institute of Neurosciences, University of Padua, Via Ugo Bassi 58/B, 35121 Padova, Italy.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Pinna
authors.affiliation: Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany. Electronic address: uwe.knippschild@uniklinik-ulm.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knippschild
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism*
chemical_list: D010455:Peptides; D014404:Tubulin; D017346:Protein Serine-Threonine Kinases
keywords: CK1; Microtubules; Mitosis; Peptide therapeutics