Abstract
Abnormal amplification of centrosomes could lead to improper chromosome segregation and aneuploidy and is implicated in cancer development. Here, we demonstrate that Axin, a scaffolding protein in Wnt signaling, is phosphorylated by PLK1 during mitosis. Phosphorylation of Axin Ser-157 by PLK1 abolished Axin association with γ-tubulin, while substitution of Ser-157 with alanine exhibited sustained interaction with γ-tubulin. In addition, overexpression of Axin-S157A significantly increased the number of cells with multi-centrosomes. These results suggest that the phosphorylation status of Axin, mediated by PLK1, dynamically regulates its association with γ-tubulin and centrosome formation and segregation.
Highlights
Centrosome defects are implicated as a primary cause of chromosomal instability and aneuploidy in cancer development [1,2,3]
When exploring biochemical consequence of the interaction between PLK1 and Axin, we found that Axin displayed an up-shift in mobility on the SDS-PAGE gel when co-expressed with PLK1, whereas Axin2 did not show such a mobility shift (Figure 1A)
Axin coexpressed with wild-type (WT) PLK1 but not kinase dead K82M mutant (DN) PLK1 had a slower mobility on the gel, compared to that co-expressed with a control vector
Summary
Centrosome defects are implicated as a primary cause of chromosomal instability and aneuploidy in cancer development [1,2,3]. Abnormal increase in the number of centrosome can adversely affect spindle function and cytokinesis, leading to the formation of multi-polar spindles that promote chromosome missegregation and polyploidy, and genetic instability [4,5]. Polo-like kinases (PLK) play key roles during multiple stages of mitosis, from prophase to cytokinesis [6,7]. Overexpression of PLK1 in tumors is frequently associated with DNA aneuploidy and centrosome amplification. Knockdown of PLK1 by small interference RNAs (siRNAs) suppresses centrosome amplification [11,12]
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