GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:16254014
| Citation |
Khan, OY, Fu, G, Ismail, A, Srinivasan, S, Cao, X, Tu, Y, Lu, S and Nawaz, Z (2006) Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. Mol. Endocrinol. 20:544-59 |
|---|---|
| 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 wild-type 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. |
| Links |
PubMed Online version:10.1210/me.2005-0110 |
| Keywords |
Androgen-Binding Protein/genetics; Animals; Apoptosis/genetics; Caspases/genetics; Caspases/metabolism; Cyclin-Dependent Kinase Inhibitor p21/genetics; Cyclin-Dependent Kinase Inhibitor p21/metabolism; Gene Expression Regulation, Developmental; Male; Mice; Mice, Mutant Strains; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; Promoter Regions, Genetic; Prostate/growth & development; Prostate/pathology; Prostate/physiology; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; Receptors, Androgen/genetics; Receptors, Androgen/metabolism; Testosterone/metabolism; Transcription, Genetic; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism; bcl-2-Associated X Protein/genetics; bcl-2-Associated X Protein/metabolism; rhoA GTP-Binding Protein/genetics; rhoA GTP-Binding Protein/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0006511: ubiquitin-dependent protein catabolic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0045944: positive regulation of transcription by RNA polymerase II |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:88064 |
P |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0060736: prostate gland growth |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2181811 |
P |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0014068: positive regulation of phosphatidylinositol 3-kinase signaling |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2181811 |
P |
Seeded From UniProt |
complete | ||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:P19091 |
F |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0030521: androgen receptor signaling pathway |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:P19091 |
P |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0045944: positive regulation of transcription by RNA polymerase II |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0045944: positive regulation of transcription by RNA polymerase II |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:105098 |
P |
Seeded From UniProt |
complete | ||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O08759 |
F |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0030521: androgen receptor signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0033144: negative regulation of intracellular steroid hormone receptor signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
acts_upstream_of_or_within |
GO:0045944: positive regulation of transcription by RNA polymerase II |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:105098 |
P |
has_regulation_target:(MGI:MGI:102849) |
Seeded From UniProt |
complete | |
|
enables |
GO:0003700: DNA-binding transcription factor activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
|
acts_upstream_of_or_within |
GO:0045944: positive regulation of transcription by RNA polymerase II |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
acts_upstream_of_or_within |
GO:0030521: androgen receptor signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
acts_upstream_of_or_within |
GO:0033144: negative regulation of intracellular steroid hormone receptor signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
acts_upstream_of_or_within |
GO:0060736: prostate gland growth |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2181811 |
P |
occurs_in:(EMAPA:19287) |
Seeded From UniProt |
complete | |
|
acts_upstream_of_or_within |
GO:0045944: positive regulation of transcription by RNA polymerase II |
ECO:0000316: genetic interaction evidence used in manual assertion |
MGI:MGI:88064 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0030521: androgen receptor signaling pathway |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P19091 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0014068: positive regulation of phosphatidylinositol 3-kinase signaling |
ECO:0000315: mutant phenotype evidence used in manual assertion |
MGI:MGI:2181811 |
P |
Seeded From UniProt |
complete | ||
|
acts_upstream_of_or_within |
GO:0006511: ubiquitin-dependent protein catabolic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0003713: transcription coactivator activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
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