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:3.4.21.73 (
urokinase-type plasminogen activator
)
10,685
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The mRNAs of
urokinase plasminogen activator
(
uPA
) and its receptor, uPAR, contain instability-determining AU-rich elements (AREs) in their 3' untranslated regions. The cellular proteins binding to these RNA sequences (ARE(
uPA
/uPAR)) are not known. We show here that the mRNA-stabilizing factor HuR functionally interacts with these sequences. HuR stabilized an ARE(
uPA
)-containing RNA substrate in vitro and stabilized in HeLa Tet-off cells both endogenous
uPA
and uPAR mRNAs and a beta-globin reporter mRNA containing the ARE(
uPA
). RNAi-mediated depletion of HuR in BT-549 and MDA-MB-231 cells significantly reduced the steady-state levels of endogenous
uPA
and uPAR mRNAs. Furthermore, we show that a constitutively active form of
mitogen-activated protein kinase-activated protein kinase 2
(
MK2
),
MK2
-EE, has an ARE-mRNA-stabilizing effect that correlates with its ability to enhance the cytoplasmic accumulation of endogenous HuR, but not in cells cotransfected with a dominant negative version of
MK2
,
MK2
-K76R. These effects were mimicked by hydrogen peroxide treatment (oxidative stress), which resulted in the phosphorylation of endogenous
MK2
. In addition, hydrogen peroxide treatment enhanced the cytoplasmic binding of HuR to the ARE(
uPA
), which was abrogated in cells transfected with
MK2
-K76R. These results indicate a role for HuR and
MK2
in regulating the expression of
uPA
and uPAR genes at the posttranscriptional level.
...
PMID:Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2. 1451 88
