Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland

Obaid Y. Khan, Guilian Fu, Ayesha Ismail, Sathish Srinivasan, Xuni Cao, Yaping Tu, Shan Lu, Zafar Nawaz

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Abstract

In this study we report that deletion of E6-associated protein (E6-AP) in mice results in a smaller prostate gland compared with that in normal wildtype animals. To investigate the mechanism(s) by which E6-AP affects prostate gland growth and development, we carried out both in vitro and in vivo experiments. In this study we show that E6-AP interacts with androgen receptor (AR) in a hormone-dependent manner and enhances the transactivation function of AR. Our in vivo data from E6-AP-null prostate glands show that the level of AR protein is elevated while the level of the AR target protein, probasin, is decreased. In contrast, the level of AR protein is decreased, and its target protein is increased in an E6-AP-overexpressing stable cell line, suggesting that E6-AP modulates both the protein level and the activity of AR. In addition, we show that the levels of phosphatidylinositol 3-kinase, total Akt, and phosphorylated Akt are decreased in E6-AP-null prostate, suggesting that E6-AP deletion down-regulates the signaling of the phosphatidylinositol 3-kinase-Akt pathway. We also show that RhoA negatively regulates AR function, and RhoA levels are increased in E6-AP-null prostate. Furthermore, expression levels of p53, Bax, active caspases, and apoptotic index are increased in E6-AP-null prostate. Collectively, our data suggest that E6-AP deletion attenuates the growth and development of the prostate gland by interfering with AR function as well as by stimulating p53-mediated apoptosis.

Original languageEnglish
Pages (from-to)544-559
Number of pages16
JournalMolecular Endocrinology
Volume20
Issue number3
DOIs
StatePublished - Mar 2006

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Steroid Receptors
Prostate
Androgen Receptors
Proteins
Phosphatidylinositol 3-Kinase
Growth and Development
Caspases
Transcriptional Activation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. / Khan, Obaid Y.; Fu, Guilian; Ismail, Ayesha; Srinivasan, Sathish; Cao, Xuni; Tu, Yaping; Lu, Shan; Nawaz, Zafar.

In: Molecular Endocrinology, Vol. 20, No. 3, 03.2006, p. 544-559.

Research output: Contribution to journalArticle

Khan, Obaid Y. ; Fu, Guilian ; Ismail, Ayesha ; Srinivasan, Sathish ; Cao, Xuni ; Tu, Yaping ; Lu, Shan ; Nawaz, Zafar. / Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. In: Molecular Endocrinology. 2006 ; Vol. 20, No. 3. pp. 544-559.
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