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

Shu-Er ChowChia-Chi HsuCheng-Ta YangYaa-Jyuhn James Meir
Published in: The FEBS journal (2023)
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 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 of α -tubulin and increase of 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 of 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.
Keyphrases
  • cell cycle
  • gene expression
  • cell proliferation
  • dna methylation
  • copy number
  • heat stress
  • heat shock