Τίτλος:
New potential peptide therapeutics perturbing CK1δ/α-tubulin interaction
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2016 Elsevier Ireland Ltd.
Συγγραφείς:
Krüger, M.
Kalbacher, H.
Kastritis, P.L.
Bischof, J.
Barth, H.
Henne-Bruns, D.
Vorgias, C.
Sarno, S.
Pinna, L.A.
Knippschild, U.
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
alpha tubulin; beta tubulin; casein kinase Idelta; peptide P39; protein serine threonine kinase; protein serine threonine kinase inhibitor; unclassified drug; peptide; protein binding; protein serine threonine kinase; tubulin, amino acid sequence; antiproliferative activity; Article; controlled study; drug targeting; enzyme activity; enzyme linked immunosorbent assay; eukaryote; fluorescence analysis; human; human cell; microtubule; mitosis inhibition; molecular docking; peptide analysis; peptide library; priority journal; protein binding; protein expression; protein family; protein interaction; protein phosphorylation; protein stability; protein structure; surface plasmon resonance; thermodynamics; cell proliferation; drug effects; genetics; HeLa cell line; HT 29 cell line; metabolism; mitosis; Neoplasms; pathology; phosphorylation, Cell Proliferation; HeLa Cells; HT29 Cells; Humans; Microtubules; Mitosis; Neoplasms; Peptides; Phosphorylation; Protein Binding; Protein Stability; Protein-Serine-Threonine Kinases; Tubulin
DOI:
10.1016/j.canlet.2016.03.021
