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:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Akt/protein kinase B is a pivotal component downstream of phosphatidylinositol 3-kinase (PI3K) pathway, whose activity regulates the balance between cell survival and apoptosis. Phosphorylation of Akt occurs at two key sites either at Thr308 site in the activation loop or at Ser473 site in the hydrophobic motif. The phosphorylated form of Akt (pAkt) is activated to promote cell survival. The mechanisms of pAkt dephosphorylation and how the signal transduction of Akt pathway is terminated are still largely unknown. In this study, we identified a novel
protein phosphatase
CSTP1
(complete s transactivated protein 1), which interacts and dephosphorylates Akt specifically at Ser473 site in vivo and in vitro, blocks cell cycle progression and promotes cell apoptosis. The effects of
CSTP1
on cell survival and cell cycle were abrogated by depletion of phosphatase domain of
CSTP1
or by expression of a constitutively active form of Akt (S473D), suggesting Ser473 site of Akt as a primary cellular target of
CSTP1
. Expression profile analysis showed that
CSTP1
expression is selectively down-regulated in non-invasive bladder cancer tissues and over-expression of
CSTP1
suppressed the size of tumors in nude mice. Kaplan-Meier curves revealed that decreased expression of
CSTP1
implicated significantly reduced recurrence-free survival in patients suffered from non-invasive bladder cancers.
...
PMID:CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell apoptosis, and suppresses tumor growth of bladder cancer by directly dephosphorylating Akt at Ser473 site. 2379 35
