PXD002861 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-09-07 02:07:11 | ID requested | |
⏵ 1 | 2016-07-20 03:01:26 | announced | |
Publication List
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] |
Keyword List
curator keyword: Biomedical |
submitter keyword: androgen, androgen receptor, transcription, prostate cancer, mass spectrometry-based proteomics, intracellular trafficking, protein trafficking, Golgi membrane |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/07/PXD002861 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD002861
- Label: PRIDE project
- Name: Ligand-dependent interaction networks linked to androgen receptor function in prostate-tumor cells