Normal and prostate cancer cells display distinct molecular profiles of alpha-tubulin posttranslational modifications.
BACKGROUND
Multiple diverse posttranslational modifications of alpha-tubulin such as detyrosination, further cleavage of the penultimate glutamate residue (Delta2-tubulin), acetylation, and polyglutamylation increase the structural and functional diversity of microtubules.


METHODS
Herein, we characterized the molecular profile of alpha-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 CWR22Rv1), 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 alpha-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 Delta2-tubulin. Whereas alpha-tubulin acetylation levels were generally equivalent in all the cell lines, PC3 cells did not display detectable levels of Ac-tubulin.


CONCLUSIONS
These data may reveal novel biomarkers of prostate cancer and new therapeutic targets.
Department of Internal Medicine, University of California, Davis, California 95616, USA.
Karel
K
Soucek
Andrés
A
Kamaid
Anh D
AD
Phung
Lukás
L
Kubala
J Chloë
JC
Bulinski
Richart W
RW
Harper
Jason P
JP
Eiserich
D000107:Acetylation; D000728:Androgens / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D010453:Peptide Synthases / Q000032:analysis / Q000378:metabolism; D011099:Polyglutamic Acid / Q000032:analysis; D011467:Prostate / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D011944:Receptors, Androgen / Q000032:analysis; D014404:Tubulin / Q000032:analysis* / Q000378:metabolism*; D014443:Tyrosine / Q000032:analysis
D000728:Androgens; D011944:Receptors, Androgen; D014404:Tubulin; D011099:Polyglutamic Acid; D014443:Tyrosine; D010453:Peptide Synthases; C023213:tyrosyltubulin ligase