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Keywords: LMTK3; Kinase inhibitor; Breast cancer; Tubulin; NUSAP1 EN LMTK3 Kinase inhibitor Breast cancer Tubulin NUSAP1 1 6 6 12/02/21 20211201 NES 211201 The original online version of this article was revised: There are errors in Figures 2a and 2d. In addition, to confirm the involvement of NUSAP1 in the C28-mediated effect on microtubule stability and cell cycle arrest, we investigated the levels of cyclin-dependent kinase 1 (CDK1), a previously described NUSAP1-regulated protein [[12]], and phospho- III tubulin (S172). Taken together, although C28 can potentially bind tubulin, its relatively low binding affinity to purified tubulin dimer and the lack of any observable effect on tubulin polymerization suggest that C28 does not confer its effects by direct inhibition of tubulin polymerization. Considering the role of kinase inhibitors on microtubules [[4]], we investigated the possibility that C28 is a direct tubulin-targeting agent by employing an in vitro tubulin polymerization assay. [Extracted from the article]

Abstract: Kinases play a critical role in regulating many cellular functions including development, differentiation and proliferation. To date, over 518 proteins with kinase activity, comprising ~2–3% of total cellular proteins, have been identified from within the human kinome. Interestingly, approximately 10% of kinases are categorised as pseudokinases since they lack one or more conserved catalytic residues within their kinase domain and were originally thought to have no enzymatic activity. Recently, there has been strong evidence to suggest that some pseudokinsases can not only function as scaffold proteins, but may also possess kinase activity leading to modulation of cell signalling pathways. Altered activity of these pseudokinases can result in impaired cellular function, particularly in malignancies. In this review we are discussing recent evidence that apart from a scaffolding role, pseudokinases also orchestrate cellular processes as active kinases per se in signalling pathways of malignant cells. [Copyright &y& Elsevier]