PMID:21909421

Citation	Haile, S, Lal, A, Myung, JK and Sadar, MD (2011) FUS/TLS is a co-activator of androgen receptor in prostate cancer cells. PLoS ONE 6:e24197
Abstract	Androgen receptor (AR) is a member of the nuclear receptor family of transcription factors. Upon binding to androgens, AR becomes transcriptionally active to regulate the expression of target genes that harbor androgen response elements (AREs) in their promoters and/or enhancers. AR is essential for the growth and survival of prostate cancer cells and is therefore a target for current and next-generation therapeutic modalities against prostate cancer. Pathophysiologically relevant protein-protein interaction networks involving AR are, however, poorly understood. In this study, we identified the protein FUsed/Translocated in LipoSarcoma (FUS/TLS) as an AR-interacting protein by co-immunoprecipitation of endogenous proteins in LNCaP human prostate cancer cells. The hormonal response of FUS expression in LNCaP cells was shown to resemble that of other AR co-activators. FUS displayed a strong intrinsic transactivation capacity in prostate cancer cells when tethered to basal promoters using the GAL4 system. Chromatin immunoprecipitation experiments showed that FUS was recruited to ARE III of the enhancer region of the PSA gene. Data from ectopic overexpression and "knock-down" approaches demonstrated that AR transcriptional activity was enhanced by FUS. Depletion of FUS reduced androgen-dependent proliferation of LNCaP cells. Thus, FUS is a novel co-activator of AR in prostate cancer cells.
Links	PubMed PMC3164714 Online version:10.1371/journal.pone.0024197
Keywords	Amino Acid Sequence; Androgens/pharmacology; Cell Line, Tumor; Cell Proliferation/drug effects; Gene Expression Regulation, Neoplastic/drug effects; Humans; Male; Mass Spectrometry; Molecular Sequence Data; Multiprotein Complexes/metabolism; Prostatic Neoplasms/genetics; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology; Protein Transport/drug effects; RNA-Binding Protein FUS/chemistry; RNA-Binding Protein FUS/metabolism; Receptors, Androgen/genetics; Receptors, Androgen/metabolism; Subcellular Fractions/drug effects; Subcellular Fractions/metabolism; Trans-Activators/chemistry; Trans-Activators/metabolism; Transcriptional Activation/drug effects
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FUS		GO:0005634: nucleus	ECO:0000314:		C		Figure 2. Subcellular localization of FUS in prostate cancer cells	complete CACAO 2130
HUMAN:FUS		GO:0003713: transcription coactivator activity	ECO:0000314:		F		Figure 1 establishes that FUS is complexed with AR. Figure 3 demonstrates that FUS possesses innate ability to regulate transcription. Figure 4 demonstrates that FUS modulates AR activity.	complete CACAO 2132
HUMAN:FUS	part_of	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:FUS	enables	GO:0003713: transcription coactivator activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete

References

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