GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16254014

From GONUTS
Jump to: navigation, search
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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:UBE3A

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:UBE3A

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

MOUSE:UBE3A

involved_in

GO:0060736: prostate gland growth

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2181811

P

Seeded From UniProt

complete

MOUSE:UBE3A

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

MOUSE:UBE3A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P19091

F

Seeded From UniProt

complete

MOUSE:UBE3A

involved_in

GO:0030521: androgen receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

PR:P19091

P

Seeded From UniProt

complete

MOUSE:ANDR

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

MOUSE:ANDR

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

MOUSE:ANDR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O08759

F

Seeded From UniProt

complete

MOUSE:RHOA

involved_in

GO:0030521: androgen receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RHOA

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

MOUSE:ANDR

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

MOUSE:ANDR

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:ANDR

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

MOUSE:RHOA

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

MOUSE:RHOA

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

MOUSE:UBE3A

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

MOUSE:UBE3A

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

MOUSE:UBE3A

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

MOUSE:UBE3A

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

MOUSE:UBE3A

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

MOUSE:UBE3A

enables

GO:0003713: transcription coactivator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.