Linked Life Data

17220478

Source:http://linkedlifedata.com/resource/pubmed/id/17220478

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-4-9
pubmed:abstractText
NDRG1 is known to play important roles in both androgen-induced cell differentiation and inhibition of prostate cancer metastasis. However, the proteins associated with NDRG1 function are not fully enumerated. Using coimmunoprecipitation and mass spectrometry analysis, we identified 58 proteins that interact with NDRG1 in prostate cancer cells. These proteins include nuclear proteins, adhesion molecules, endoplasmic reticulum (ER) chaperons, proteasome subunits, and signaling proteins. Integration of our data with protein-protein interaction data from the Human Proteome Reference Database allowed us to build a comprehensive interactome map of NDRG1. This interactome map consists of several modules such as a nuclear module and a cell membrane module; these modules explain the reported versatile functions of NDRG1. We also determined that serine 330 and threonine 366 of NDRG1 were phosphorylated and demonstrated that the phosphorylation of NDRG1 was prominently mediated by protein kinase A (PKA). Further, we showed that NDRG1 directly binds to beta-catenin and E-cadherin. However, the phosphorylation of NDRG1 did not interrupt the binding of NDRG1 to E-cadherin and beta-catenin. Finally, we showed that the inhibition of NDRG1 expression by RNA interference decreased the ER inducible chaperon GRP94 expression, directly proving that NDRG1 is involved in the ER stress response. Intriguingly, we observed that many members of the NDRG1 interactome are androgen-regulated and that the NDRG1 interactome links to the androgen response network through common interactions with beta-catenin and heat shock protein 90. Therefore we overlaid the transcriptomic expression changes in the NDRG1 interactome in response to androgen treatment and built a dual dynamic picture of the NDRG1 interactome in response to androgen. This interactome map provides the first road map for understanding the functions of NDRG1 in cells and its roles in human diseases, such as prostate cancer, which can progress from androgen-dependent curable stages to androgen-independent incurable stages.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1535-9476
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-88
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17220478-Androgens, pubmed-meshheading:17220478-Cadherins, pubmed-meshheading:17220478-Cell Cycle Proteins, pubmed-meshheading:17220478-Cell Line, Tumor, pubmed-meshheading:17220478-Endoplasmic Reticulum, pubmed-meshheading:17220478-Humans, pubmed-meshheading:17220478-Immunoprecipitation, pubmed-meshheading:17220478-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17220478-Male, pubmed-meshheading:17220478-Models, Biological, pubmed-meshheading:17220478-Neoplasms, Hormone-Dependent, pubmed-meshheading:17220478-Phosphorylation, pubmed-meshheading:17220478-Prostatic Neoplasms, pubmed-meshheading:17220478-Protein Binding, pubmed-meshheading:17220478-Protein Interaction Mapping, pubmed-meshheading:17220478-Proteomics, pubmed-meshheading:17220478-Tandem Mass Spectrometry, pubmed-meshheading:17220478-beta Catenin
pubmed:year
2007
pubmed:articleTitle
Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and its interactions with the androgen response program in prostate cancer cells.
pubmed:affiliation
Institute for Systems Biology, Seattle, Washington 98103, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural