Diazonamide toxins reveal an unexpected function for ornithine δ-amino transferase in mitotic cell division

Gelin Wang, Libin Shang, Anthony W G Burgett, Patrick G. Harran, Xiaodong Wang

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

We have studied a naturally occurring small-molecule antimitotic called diazonamide A. Diazonamide A is highly effective at blocking spindle assembly in mammalian cell culture and does so through a unique mechanism. A biotinylated form of diazonamide A affinity purifies ornithine δ-amino transferase (OAT), a mitochondrial enzyme, from HeLa cell and Xenopus egg extracts. In the latter system, the interaction between diazonamide A and OAT is regulated by RanGTP. We find that specific OAT knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death, the effects largely phenocopying diazonamide A treatment in these cell lines. Our experiments reveal an unanticipated, paradoxical role for OAT in mitotic cell division and identify the protein as a target for chemotherapeutic drug development.

Original languageEnglish (US)
Pages (from-to)2068-2073
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number7
DOIs
StatePublished - Feb 13 2007

Keywords

  • Mitochondria
  • Mitosis
  • Mitotic spindle
  • Natural
  • Product

ASJC Scopus subject areas

  • General

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