The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities

Hung Ju Shih, Kang Lin Chu, Meng Hsun Wu, Pei Hsuan Wu, Wei Wen Chang, Jan Show Chu, Lily Hui Ching Wang, Hideki Takeuchi, Toru Ouchi, Hsin Ling Hsu

研究成果: 雜誌貢獻文章同行評審

5 引文 斯高帕斯(Scopus)

摘要

Centrosome amplification and chromosome abnormality are frequently identified in neoplasia and tumorigenesis. However, the mechanisms underlying these defects remain unclear. Here, we identify that MCT-1 is a centrosomal oncoprotein involved in mitosis. Knockdown of MCT-1 protein results in intercellular bridging, chromosome miscongregation, cytokinesis delay and mitotic death. Introduction of MCT-1 oncogene into the p53 deficient cells (MCT-1-p53), the mitotic checkpoint kinases and proteins are deregulated synergistically. These biochemical alterations are accompanied with increased frequencies of cytokinesis failure, multi-nucleation and centrosome amplification in subsequent cell cycle. As a result, the incidences of polyploidy and aneuploidy are progressively induced by prolonged cell cultivation or further promoted by sustained spindle damage on MCT-1-p53 background. These data show that the oncoprotein perturbs centrosome structure and mitotic progression, which provide the molecular aspect of chromsomal abnormality in vitro and the information for understanding the stepwise progression of tumors under oncogenic stress.

原文英語
頁(從 - 到)934-952
頁數19
期刊Cell Cycle
11
發行號5
DOIs
出版狀態已發佈 - 三月 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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