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:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The importance of
ornithine decarboxylase
(
ODC
) to cell proliferation is underscored by the complex array of cell-specific mechanisms invoked to regulate its synthesis and activity. Misregulation of
ODC
has severe negative consequences on normal cell function, including the acquisition of tumorigenic growth properties by cells overexpressing
ODC
. We hypothesize that
ODC
gene expression is a candidate target for the anti-proliferative function of certain tumor suppressors. Here we show that the
Wilms' tumor suppressor
WT1 binds to multiple sites within the human
ODC
promoter, as determined by DNase I protection and methylation interference assays. The expression of WT1 in transfected HCT 116, NIH/3T3 and HepG2 cells represses activity of the
ODC
promoter controlling expression of a luciferase reporter gene. In contrast WT1 expression enhances
ODC
promoter activity in SV40-transfected HepG2 cells. Both the extent of modulation of
ODC
gene expression and the mediating WT1 binding elements are cell specific. Constructs expressing WT1 deletion mutants implicate two regions required for repressor function, as well as an intrinsic activation domain. Understanding the regulation of
ODC
gene expression by WT1 may provide valuable insights into the roles of both WT1 and
ODC
in development and tumorigenesis.
...
PMID:Regulation of ornithine decarboxylase gene expression by the Wilms' tumor suppressor WT1. 860 51
