Nucleoside diphosphate kinase Nm23-H1 regulates chromosomal stability by activating the GTPase dynamin during cytokinesis

Andrew R. Conery, Sanja Sever, Ed Harlow

Research output: Contribution to journalArticlepeer-review

Abstract

Chromosomal instability and the subsequent genetic mutations are considered to be critical factors in the development of themajority of solid tumors. Here, we describe how the nucleoside diphosphate kinase Nm23-H1, a protein with a known link to cancer progression, regulates a critical step during cytokinesis. Nm23-H1 acts to provide a local source of GTP for the GTPase dynamin. Loss of Nm23-H1 in diploid cells leads to cytokinetic furrow regression, followed by cytokinesis failure and generation of tetraploid cells. Loss of dynamin phenocopies loss of Nm23-H1, and ectopic overexpression of WT dynamin complements the loss of Nm23-H1. In the absence of p53 signaling, the tetraploidcells resulting from loss of Nm23-H1 continue cycling and develop classic hallmarks of tumor cells. We thus provide evidence that the loss of Nm23-H1, an event suspected to promote metastasis, may additionally function at an earlier stage of tumor development to drive the acquisition of chromosomal instability.

Original languageEnglish (US)
Pages (from-to)15461-15466
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number35
DOIs
StatePublished - Aug 31 2010
Externally publishedYes

Keywords

  • Aneuploidy
  • Cell cycle
  • p53
  • RNAi screen
  • Tetraploidy

ASJC Scopus subject areas

  • General

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