YAP co‐localizes with the mitotic spindle and midbody to safeguard mitotic division in lung‐cancer cells

Abstract

YES‐associated protein (YAP) is a part of the Hippo pathway, with pivotal roles in several developmental processes and dual functionality as both a tumor suppressor and an oncogene. In the present study, we identified YAP activity as a microtubular scaffold protein that maintains the stability of the mitotic spindle and midbody by physically interacting with α‐tubulin during mitotic progression. The interaction of YAP and α‐tubulin was evident in co‐immunoprecipitation assays, as well as observing their co‐localization in the microtubular structure of the mitotic spindle and midbody in immunostainings. With YAP depletion, levels of ECT2, MKLP‐1, and Aurora B are reduced, which is consistent with YAP functioning in midbody formation during cytokinesis. The concomitant decrease in α‐tubulin and increase in acetyl‐α‐tubulin during YAP depletion occurred at the post‐transcriptional level. This suggests that YAP maintains the stability of the mitotic spindle and midbody, which ensures appropriate chromosome segregation during mitotic division. The increase in acetyl‐α‐tubulin during YAP depletion may provide a lesion‐halting mechanism in maintaining the microtubule structure. The depletion of YAP also results in multinuclearity and aneuploidy, which supports its role in stabilizing the mitotic spindle and midbody.