Characterization of nuclear βII-tubulin in tumor cells: A possible novel target for taxol

Keliang Xu, Richard F. Ludueña

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

As the subunits of microtubules, α- and β-tubulins have been thought to only exist in the cytoplasm where they are incorporated into microtubules. However, the βII isotype of tubulin has recently been observed in the nuclei of rat kidney mesangial cells [Walss et al., 1999: Cell Motil. Cytoskeleton 42:274-284]. In this study, we detected nuclear βII-tubulin in rat C6 glioma cells, human T98G glioma cells, human MCF-7 breast carcinoma cells, human MDA-MB-435 breast carcinoma cells, and human Hela cervix carcinoma cells. In addition, nuclear βII-tubulin in these cells was found to exist as αβII dimers instead of assembled microtubules and appeared to be particularly concentrated in the nucleoli. Several anti-tubulin drugs were used to treat C6 cells to determine their influence on nuclear βII-tubulin. Taxol, a tubulin drug with higher specificity for βII-tubulin than for other β-tubulin isotypes, irreversibly decreased nuclear βII content in a concentration-dependent manner in C6 cells. Meanwhile, cells were found to be apoptotic as was suggested by the presence of multiple micronuclei and DNA fragmentation. On the other hand, no depletion of nuclear βII-tubulin was observed when C6 cells were incubated with colchicine or nocodazole, two anti-tubulin drugs with higher specificity for the αβIV isotype, supporting the hypothesis that drugs with higher specificity for βII-tubulin deplete nuclear βII-tubulin.

Original languageEnglish (US)
Pages (from-to)39-52
Number of pages14
JournalCell Motility and the Cytoskeleton
Volume53
Issue number1
DOIs
StatePublished - Sep 2002

Keywords

  • Apoptosis
  • Isotypes
  • Nuclear structure
  • Taxol
  • Tubulin

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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