DVL3 peptide

Primary cilia are organelles necessary for proper implementation of developmental and homeostasis processes. To initiate their assembly, coordinated actions of multiple proteins are needed. Tau tubulin kinase 2 (TTBK2) is a key player in the cilium assembly pathway, controlling the final step of cilia initiation. The function of TTBK2 in ciliogenesis is critically dependent on its kinase activity; however, the precise mechanism of TTBK2 action has so far not been fully understood due to the very limited information about its relevant substrates. In this study, we demonstrate that CEP83, CEP89, CCDC92, Rabin8, and DVL3 are substrates of TTBK2 kinase activity. Further, we characterize a set of phosphosites of those substrates and CEP164 induced by TTBK2 in vitro and in vivo. Intriguingly, we further show that identified TTBK2 phosphosites and consensus sequence delineated from those are distinct from motifs previously assigned to TTBK2. Finally, we show that TTBK2 is also required for efficient phosphorylation of many S/T sites in CEP164 and provide evidence that TTBK2-induced phosphorylations of CEP164 modulate its function, which in turn seems relevant for the process of cilia formation. In summary, our work provides important insight into the substrates-TTBK2 kinase relationship and suggests that phosphorylation of substrates on multiple sites by TTBK2 is probably involved in the control of ciliogenesis in human cells.

Background: The aim of the current study was to screen differentially-expressed genes (DEGs) relevant to cancer progression and prognosis of squamous cell lung carcinoma (SqCLC). Methods: DEGs mRNA expression data of SqCLC was screened from the Oncomine database. This data was further analyzed by comparing tumor tissues to normal tissues. Prognostic values of DEGs relevant to SqCLC were investigated using the "Kaplan-Meier Plotter" (KM plotter) database. Bioinformation for included genes was analyzed by gene GO and KEGG enrichment, aiming to explain the potential roles of identified genes in SqCLC. Protein-protein interaction (PPI) of the genes was evaluated using the STRING database. Results: Four independent microarray datasets relevant to SqCLC were identified in the Oncomine database, with the top 10 consistently upregulated and top 10 consistently downregulated genes included in the present analysis. Significant differences of overall survival (OS) were correlated with SMC4, HIST2H2AA3, GMPS, CKS1B, POLR2H, PDCD10, PLOD2, DVL3, C-type CLEC3B, TNNC1, FAM107A, FYR, MEF2C, SLIT3, CX3CR1, C17orf91, LIM, and LIMCH1 (all P < 0.05). Possible protein-protein interaction analysis of the top 20 dysregulated genes showed that proteins of SMC4, POLR2H, and NCBP2 in upregulated genes and TNNC1 and MEF2C in downregulated genes interacted with more than 5 other proteins. This may play an important role in the development of SqCLC. Conclusion: MC4, POLR2H. TNNC1, and MEF2C genes were dysregulated in SqCLC. Thus, they may play an essential role in the development of SqCLC, as biomarkers for patient prognosis.