PXD002861

PXD002861 is an original dataset announced via ProteomeXchange.

Title	Ligand-dependent interaction networks linked to androgen receptor function in prostate-tumor cells
Description	Aberrant activation of androgen receptor (AR)-dependent transcriptional programs is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions (PPIs) involving AR-interacting proteins, which we designate the “AR-interactome”. Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate-tumor cells has not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate-tumor cell line, N-AR, which stably expresses wild-type AR containing the streptavidin-binding peptide epitope tagged at its N-terminus (SBP-AR). A bioanalytical workflow involving streptavidin-chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive proteins/protein complexes functionally linked to AR activation in the cytosol of N-AR cells. Functional studies verified that ligand-sensitive streptavidin-copurified proteins encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive COPI retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI-retrograde complex regulates ligand-mediated AR transcriptional activation through the mobilization of Golgi-localized ARA160 coactivator into the nuclear compartment of prostate-tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate-tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers.
HostingRepository	PRIDE
AnnounceDate	2016-07-20
AnnouncementXML	Submission_2016-07-20_03:01:25.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jordy Hsiao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	6520 Quadrupole Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-07 02:07:11	ID requested
⏵ 1	2016-07-20 03:01:26	announced

Hsiao JJ, Smits MM, Ng BH, Lee J, Wright ME, Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription. J Biol Chem, 291(36):18818-42(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: androgen, androgen receptor, transcription, prostate cancer, mass spectrometry-based proteomics, intracellular trafficking, protein trafficking, Golgi membrane

Michael Eugene Wright
contact affiliation	Molecular Physiology & Biophysics Department, Wright Lab, University of Iowa, USA
contact email	michael-e-wright@uiowa.edu
lab head
Jordy Hsiao
contact affiliation	University of Iowa
contact email	jordy-hsiao@uiowa.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002861
     1. Label: PRIDE project
     2. Name: Ligand-dependent interaction networks linked to androgen receptor function in prostate-tumor cells