RGD Reference Report - A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity. - Rat Genome Database

RGD Reference Report - A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity. - Rat Genome Database

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General

A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity.
Authors:	Kawashima, H Takano, H Sugita, S Takahara, Y Sugimura, K Nakatani, T
Citation:	Kawashima H, etal., Biochem J 2003 Jan 1;369(Pt 1):163-71.
RGD ID:	628587
Pubmed:	PMID:12350225 (View Abstract at PubMed)
PMCID:	PMC1223065 (View Article at PubMed Central)
DOI:	DOI:10.1042/BJ20020743 (Journal Full-text)
We have cloned a cDNA coding for a novel steroid receptor co-activator protein termed SRAP from a rat prostate library. Although the nucleotide sequence of the SRAP has 78.2% identity to that of the human steroid receptor RNA activator (SRA), a novel RNA molecule which was reported to act as an RNA transcript without being translated into protein [Lanz, McKenna, Onate, Albrecht, Wong, Tsai, Tsai and O'Malley (1999) Cell 97, 17-27], the cDNA of SRAP is capable of generating a functional protein. Glutathione S-transferase pull-down assays showed that SRAP associates with the partial androgen receptor (AR) protein composed of a DNA-binding domain and an activation function 2. Luciferase assays demonstrated that SRAP enhances the transactivation activity of the AR, the glucocorticoid receptor and the peroxisome proliferator-activated receptor gamma(1) in a ligand-dependent manner. Using a green fluorescent protein (GFP) fusion-protein construct, we demonstrated in vivo translation of the GFP-SRAP fusion protein in HeLa cells co-transfected with pSG5AR and reporter gene in the presence of 5 alpha-dihydrotestosterone (DHT). Co-transfection of the GFP-SRAP fusion protein expression plasmid enhanced the transactivation activity of AR whereas incorporation of mutations in SRAP of the fusion protein resulted in loss of enhancement of the transactivation activity. Northern blot analysis and reverse transcriptase PCR assays showed that SRAP and SRA are expressed in rat and human prostate cancer cell lines respectively. In HeLa cells and the human prostate cancer cells line DU-145, co-transfected with SRAP, the DHT-dependent transactivation activities of AR were not completely inhibited by the anti-androgen flutamide, but the transactivation activities still remained high even in the presence of 5 microM flutamide, suggesting that SRAP may play an important role in enhancing AR activity in prostate cancer.

Gene Ontology Annotations Click to see Annotation Detail View

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
nuclear receptor binding		IPI	Ar (Rattus norvegicus)	628587		RGD
nuclear receptor coactivator activity		IDA		628587		RGD
protein binding	enables	IPI	UniProtKB:Q6QGW5	628587	PMID:12350225	UniProt
protein binding	enables	IPI	UniProtKB:P15207	628587	PMID:12350225	UniProt
transcription coactivator activity	enables	IDA		628587	PMID:12350225	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Ar (androgen receptor)

Sra1 (steroid receptor RNA activator 1)

Additional Information