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)
IL-12 and IL-23 are produced by activated antigen-presenting cells but the two induce distinct immune responses by promoting Th1 and Th17 cell differentiation, respectively. IL-23 is a heterodimeric cytokine consisting of two subunits: p40 that is shared with IL-12 and p19 unique to IL-23. In this study, we showed that the production of IL-23 but not IL-12 was negatively regulated by protein phosphatase 2A (
PP2A
) in dendritic cells (DC).
PP2A
inhibits IL-23 production by suppressing the expression of the IL-23p19 gene. Treating DC with okadaic acid that inhibits the
PP2A
activity or knocking down the catalytic subunit of
PP2A
with siRNA enhanced IL-23 but not IL-12 production. Unlike
PP2A
, MAP kinase phosphatase-1 or
CYLD
did not show an effect on IL-23 production supporting the specificity of
PP2A
.
PP2A
-mediated inhibition requires a newly made protein that is likely responsible for bringing
PP2A
and IKKbeta together upon LPS stimulation, which then results in the termination of IKK phosphorylation. Thus, our results uncovered an important role of the
protein phosphatase
in the regulation of IL-23 production and identified
PP2A
as a previously uncharacterized inhibitor of IL-23p19 expression in DC.
...
PMID:Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A. 2040 53
The familial cylindromatosis tumour suppressor
CYLD
contains three cytoskeleton-associated protein glycine-rich (CAP-Gly) domains and a deubiquitinase domain. The tumour-suppressing function of
CYLD
has been attributed to its deubiquitinase domain, which removes lysine-63-linked polyubiquitin chains from target proteins, leading to the inhibition of cell survival and proliferation. In this study, we have detected an interaction of
CYLD
with the mitotic kinase Aurora-B. The interaction is mediated by the third CAP-Gly domain of
CYLD
and results in suppression of Aurora-B activity. Mechanistic studies reveal that the inhibition of Aurora-B activity by
CYLD
is independent of its deubiquitinase activity. Instead,
CYLD
interacts with protein phosphatase 2A (
PP2A
) and promotes the ability of
PP2A
to bind and dephosphorylate Aurora-B at threonine-232. Cylindromatosis-associated truncating mutations of
CYLD
abolish its interaction with
PP2A
, its enhancing effect on the
PP2A
/Aurora-B interaction, and its inhibitory effect on Aurora-B activity. These findings uncover Aurora-B and
PP2A
as novel binding partners of
CYLD
and suggest that
CYLD
negatively regulates Aurora-B activity through acting on the
PP2A
axis.
...
PMID:Tumour suppressor CYLD is a negative regulator of the mitotic kinase Aurora-B. 2059 89
