Dual function microtubule- And mitochondria-associated proteins mediate mitotic cell death

Leyuan Liu, Rui Xie, Chaofeng Yang, Wallace L. McKeehan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: Survival and evolution of aneuploid cells after an asymmetric segregation of chromosomes at mitosis may be the common initiating event and underlying cause of the genetic diversity and adaptability of cancers. We hypothesize that mechanisms exist to detect impending aneuploidy and prevent it before completion of an aberrant mitosis. Methods: The distribution of isoforms of C190RF5, an interactive partner with mitochondria-associated LRPPRC and tumor suppressor RASSF1A, state of spindle microtubules and mitochondrial aggregation was analyzed in synchronized mitotic cells and cells stalled in mitosis after treatment with paclitaxel. Results: C190RF5 distributed broadly across the mitotic spindle and reversibly accumulated during reversible mitotic arrest. Prolonged stabilization of microtubules caused an accumulation of a C19ORF5 product with dual MAP and MtAP properties that caused, irreversible aggregation of mitochondria and death of mitotic cells. Conclusion: Dual function microtubule-associated (MAP) and mitochondria-associated (MtAP) proteins generated by prolonged mitotic arrest trigger mitochondrial-induced mitotic cell death This is a potential mechanism to prevent minimal survivable aneuploidy resulting from an aberrant cell division and cancers in general at their earliest common origin.

Original languageEnglish (US)
Pages (from-to)393-405
Number of pages13
JournalCellular Oncology
Volume31
Issue number5
DOIs
StatePublished - Sep 17 2009

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Keywords

  • Aneuploidy
  • C19ORF5
  • Genetic instability
  • LRPPRC
  • Microtubule dynamics
  • Mitochondria aggregation
  • Mitochondrial dynamics
  • Paclitaxel
  • RASSF1A
  • Tumor suppression

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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