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:C0027819 (
neuroblastoma
)
27,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Dual specificity phosphatases are characterised by their ability to dephosphorylate both phosphotyrosine and phosphoserine/threonine residues within the one substrate. The aim of this study was to characterise the phosphatase activity of the atypical dual specificity phosphatase,
DUSP26
on MAP kinases, and to determine its expression, regulation and function in cancer cells. Overexpression and knockdown of
DUSP26
in epithelial cells and in vitro phosphatase assays were used to demonstrate that, contrary to several published reports,
DUSP26
does not act as a dual specificity phosphatase on ERK, JNK or p38 MAPKs. However, overexpression of
DUSP26
in MCF10A epithelial cells suppressed colony formation and acinar growth in 3D culture, effects dependent on its phosphatase activity, while knockdown of
DUSP26
in HOSE17.1 cells enhanced colony formation and cellular proliferation.
DUSP26
mRNA expression was reduced in
neuroblastoma
, brain and ovarian cancer cell lines. Consistent with epigenetic silencing of
DUSP26
, expression was enhanced by treatment of cells with 5-aza-2-deoxycitidine and trichostatin A, and a CpG island upstream of the
DUSP26
transcriptional start site was variably methylated in cancer cell lines. Together, these results help to clarify confusion in the literature relating to
DUSP26
substrate specificity and support recent reports that substrates other than MAPKs are the primary substrates of this phosphatase. In addition, they indicate that
DUSP26
may function as a tumour suppressor in particular cancers.
...
PMID:DUSP26 negatively affects the proliferation of epithelial cells, an effect not mediated by dephosphorylation of MAPKs. 2034 85
