Prohibitin and cofilin are intracellular effectors of transforming growth factor beta signaling in human prostate cancer cells.
A proteomic analysis was pursued to identify new signaling effectors of transforming growth factor beta1 (TGF-beta1) that serve as potential intracellular effectors of its apoptotic action in human prostate cancer cells. The androgen-sensitive and TGF-beta-responsive human prostate cancer cells, LNCaP T beta RII, were used as in vitro model. In response to TGF-beta, significant posttranslational changes in two proteins temporally preceded apoptotic cell death. TGF-beta mediated the nuclear export of prohibitin, a protein involved in androgen-regulated prostate growth, to the cytosol in the LNCaP T beta RII cells. Cofilin, a protein involved in actin depolymerization, cell motility, and apoptosis, was found to undergo mitochondrial translocation in response to TGF-beta before cytochrome c release. Loss-of-function approaches (small interfering RNA) to silence prohibitin expression revealed a modest decrease in the apoptotic response to TGF-beta and a significant suppression in TGF-beta-induced cell migration. Silencing Smad4 showed that the cellular localization changes associated with prohibitin and cofilin action in response to TGF-beta are independent of Smad4 intracellular signaling.
Zhu
Beibei
B
Division of Urology, College of Medicine, University of Kentucky, Lexington, KY 40536-0298, USA.
Fukada
Kei
K
Zhu
Haining
H
Kyprianou
Natasha
N
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051338:Cofilin 1 / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D000091402:Prohibitins; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D020543:Proteome; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology
D051338:Cofilin 1; D000091402:Prohibitins; D020543:Proteome; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D045304:Cytochromes c