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: UMLS:C0699790 (
colon cancer
)
28,837
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In search for a new anticancer drug target, we explored genes involved in colon adenocarcinoma development through dysregulation of a signal transduction pathway. By using the gene expression profile database, we found protein phosphatase 1H (
PPM1H
), belonging to the protein phosphatase 2C (PP2C) family, upregulated in colon adenocarcinomas compared with normal colon tissues. RT-PCR analysis verified the elevated level of
PPM1H
expression in
colon cancer
cell lines relative to a normal colon cell line.
PPM1H
encodes a protein with a molecular mass of approximately 50 kDa that resides in the cytoplasm.
PPM1H
fused with maltose-binding protein expressed in E. coli exhibited phosphatase activity characteristic of the PP2C family. Co-immunoprecipitation coupled with mass spectrometry analysis identified CSE1L, a proliferation and apoptosis-related protein, as a
PPM1H
-interacting protein. Native, but not inactive,
PPM1H
expressed in HeLa cells increased the mobility of CSE1L on SDS gels and a similar mobility shift was observed for purified CSE1L after treatment with
PPM1H
in vitro, supporting the notion that CSE1L is a substrate of
PPM1H
. Dominant negative
PPM1H
protected HeLa cells from cell death triggered by staurosporine or taxol. Additionally, knockdown of
PPM1H
expression with small interfering RNAs suppressed the growth of MCF-7 cells weakly but consistently.
PPM1H
controls cell cycle and proliferation of cancer cells potentially through dephosphorylation of CSE1L and might be a new target of anticancer drugs.
...
PMID:Protein phosphatase 1H, overexpressed in colon adenocarcinoma, is associated with CSE1L. 1862 3
