New potential peptide therapeutics perturbing CK1δ/α-tubulin interaction

Cancer Lett. 2016 Jun 1;375(2):375-383. doi: 10.1016/j.canlet.2016.03.021. Epub 2016 Mar 17.

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.

Keywords: CK1; Microtubules; Mitosis; Peptide therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects*
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitosis / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Peptides / administration & dosage
  • Peptides / metabolism*
  • Phosphorylation
  • Protein Binding / drug effects
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Stability / drug effects
  • Tubulin / metabolism*

Substances

  • Peptides
  • Tubulin
  • Protein Serine-Threonine Kinases