New potential peptide therapeutics perturbing CK1 delta/alpha-tubulin interaction

作者：Krueger Marc; Kalbacher Hubert; Kastritis Panagiotis L; Bischof Joachim; Barth Holger; Henne Bruns Doris; Vorgias Constantinos; Sarno Stefania; Pinna Lorenzo A; Knippschild Uwe^*

来源：Cancer Letters, 2016, 375(2): 375-383.

DOI：10.1016/j.canlet.2016.03.021

• CK1
• Mitosis
• Peptide therapeutics
• Microtubules

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. CK1 delta interacts with alpha-/beta-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 CK1 delta amino acid sequence in SPR and ELISA analyses, we identified peptide 39 (P39), encompassing aa361-aa375 of CK1 delta, as a prominent binding partner of alpha-tubulin. P39 decreases alpha-tubulin phosphorylation by CK1 delta and reduces the thermodynamic stability of alpha-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 CK1 delta and alpha-tubulin and a novel approach for the development of pharmacological tools to inhibit proliferation of cancer cells.

• 出版日期2016-6-1