Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.3.2.19 (
ubiquitin-protein ligase
)
799
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
PMEPA1
was originally identified as a highly androgen-induced gene by serial analysis of gene expression in androgen-treated LNCaP prostate cancer (CaP) cells.
PMEPA1
expression is prostate abundant and restricted to prostatic epithelial cells.
PMEPA1
-encoded protein shows high sequence homology to a mouse N4wbp4-encoded protein that binds to Nedd4 protein, an E3
ubiquitin-protein ligase
involved in ubiquitin-dependent, proteasome-mediated protein degradation. Studies from our and other laboratories have suggested the role of
PMEPA1
in cell growth regulation as noted by androgen induction of
PMEPA1
expression, elevated
PMEPA1
expression in nontumorigenic revertants of tumor cell lines after chromosome 8p transfer, and
PMEPA1
expression alterations (up- or down-regulation) in human tumors. Here, we demonstrate that PMEPA1 protein through its PY motifs interacts with WW domains of the human NEDD4 protein. Exogenous expression of
PMEPA1
, in widely used CaP cell lines DU145, PC3, LNCaP, and LNCaP sublines (C4, C4-2, and C4-2B), conferred cell growth inhibition, and at least one of the PY motifs of
PMEPA1
may be involved in its cell growth inhibitory functions. Quantitative expression analysis of
PMEPA1
in paired normal and tumor cells of 62 patients with primary CaP revealed tumor cells associated decreased expression in 40 of 62 patients that were significantly associated with higher pathologic stage and serum prostate-specific antigen. Taken together,
PMEPA1
negatively regulates growth of androgen responsive or refractory CaP cells, and these functions may be mediated through the interaction of
PMEPA1
with the NEDD4 protein involved in the ubiquitin-proteasome pathway. Loss or reduced
PMEPA1
expression in CaP further suggests for its role in prostate tumorigenesis.
...
PMID:PMEPA1, an androgen-regulated NEDD4-binding protein, exhibits cell growth inhibitory function and decreased expression during prostate cancer progression. 1290 94
