Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications

Karel Souček, Andrés Kamaid, Anh D. Phung, Lukáš Kubala, J. Chloë Bulinski, Richart W Harper, Jason P. Eiserich

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

BACKGROUND. Multiple diverse posttranslational modifications of α-tubulin such as detyrosination, further cleavage of the penultimate glutamate residue (Δ2-tubulin), acetylation, and polyglutamylation increase the structural and functional diversity of microtubules. METHODS. Herein, we characterized the molecular profile of α-tubulin posttranslational modifications in normal human prostate epithelial cells (PrEC), immortalized normal prostate epithelial cells (PZ-HPV-7), androgen-dependent prostate cancer cells (LNCaP), transitional androgen-independent prostate cancer cells (LNCaP-cds and CWR22Rυ1), and androgen-independent prostate cancer cells (PC3). RESULTS. Compared to PrEC and PZ-HPV-7 cells, all cancer cells exhibited elevated levels of detyrosinated and polyglutamylated α-tubulin, that was paralleled by decreased protein levels of tubulin tyrosine ligase (TTL). In contrast, PrEC and PZ-HPV-7 cells expressed markedly higher levels of Δ2-tubulin. Whereas α-tubulin acetylation levels were generally equivalent in all the cell lines, PC3 cells did not display detectable levels of Ac-tubulin. CONCLUSION. These data may reveal novel biomarkers of prostate cancer and new therapeutic targets.

Original languageEnglish (US)
Pages (from-to)954-965
Number of pages12
JournalProstate
Volume66
Issue number9
DOIs
StatePublished - Jun 15 2006

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Keywords

  • Acetylation
  • Detyrosination
  • HDAC6
  • Microtubules
  • Polyglutamylation
  • Prostate cancer
  • SIRT2
  • Tubulin tyrosine ligase

ASJC Scopus subject areas

  • Urology

Cite this

Souček, K., Kamaid, A., Phung, A. D., Kubala, L., Bulinski, J. C., Harper, R. W., & Eiserich, J. P. (2006). Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications. Prostate, 66(9), 954-965. https://doi.org/10.1002/pros.20416