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

59 Citations (Scopus)

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

Fingerprint

Post Translational Protein Processing
Tubulin
Prostatic Neoplasms
Prostate
Epithelial Cells
Androgens
Acetylation
Microtubules
Glutamic Acid
Biomarkers
Cell Line
Neoplasms
Proteins

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

Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications. / Souček, Karel; Kamaid, Andrés; Phung, Anh D.; Kubala, Lukáš; Bulinski, J. Chloë; Harper, Richart W; Eiserich, Jason P.

In: Prostate, Vol. 66, No. 9, 15.06.2006, p. 954-965.

Research output: Contribution to journalArticle

Souček, K, Kamaid, A, Phung, AD, Kubala, L, Bulinski, JC, Harper, RW & Eiserich, JP 2006, 'Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications', Prostate, vol. 66, no. 9, pp. 954-965. https://doi.org/10.1002/pros.20416
Souček, Karel ; Kamaid, Andrés ; Phung, Anh D. ; Kubala, Lukáš ; Bulinski, J. Chloë ; Harper, Richart W ; Eiserich, Jason P. / Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications. In: Prostate. 2006 ; Vol. 66, No. 9. pp. 954-965.
@article{1dbad24c5f7b4c9cbf3cc11fa9984a53,
title = "Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications",
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.",
keywords = "Acetylation, Detyrosination, HDAC6, Microtubules, Polyglutamylation, Prostate cancer, SIRT2, Tubulin tyrosine ligase",
author = "Karel Souček and Andr{\'e}s Kamaid and Phung, {Anh D.} and Luk{\'a}š Kubala and Bulinski, {J. Chlo{\"e}} and Harper, {Richart W} and Eiserich, {Jason P.}",
year = "2006",
month = "6",
day = "15",
doi = "10.1002/pros.20416",
language = "English (US)",
volume = "66",
pages = "954--965",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Normal and prostate cancer cells display distinct molecular profiles of α-tubulin posttranslational modifications

AU - Souček, Karel

AU - Kamaid, Andrés

AU - Phung, Anh D.

AU - Kubala, Lukáš

AU - Bulinski, J. Chloë

AU - Harper, Richart W

AU - Eiserich, Jason P.

PY - 2006/6/15

Y1 - 2006/6/15

N2 - 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.

AB - 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.

KW - Acetylation

KW - Detyrosination

KW - HDAC6

KW - Microtubules

KW - Polyglutamylation

KW - Prostate cancer

KW - SIRT2

KW - Tubulin tyrosine ligase

UR - http://www.scopus.com/inward/record.url?scp=33744901133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744901133&partnerID=8YFLogxK

U2 - 10.1002/pros.20416

DO - 10.1002/pros.20416

M3 - Article

VL - 66

SP - 954

EP - 965

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 9

ER -