New potential peptide therapeutics perturbing CK1δ/α-tubulin interaction. Issue 2 (1st June 2016)

• Record Type: Journal Article
• Authors: Krüger, Marc; Kalbacher, Hubert; Kastritis, Panagiotis L.; Bischof, Joachim; Barth, Holger; Henne-Bruns, Doris; Vorgias, Constantinos; Sarno, Stefania; Pinna, Lorenzo A.; Knippschild, Uwe
• Is Part Of: Cancer letters. Volume 375:Issue 2(2016)
• Page Start: 375
• Page End: 383
• Publication Date: 2016-06-01
• Subjects: CK1 -- Mitosis -- Peptide therapeutics -- Microtubules; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.03.021
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Identification of domains involved in the CK1δ/α-tubulin interaction. CK1δ peptide 39 (P39; aa361–aa375) as a prominent binding partner of α-tubulin. P39 reduces CK1δ mediated phosphorylation of α-tubulin and CK1δ stability. P39 induces an inhibition of mitotic progression and a disruption of mitotic cells. 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.