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:3.4.22.61 (
caspase-8
)
6,833
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
FAF1
has been introduced as a Fas-binding protein. However, the function of
FAF1
in apoptotic execution is not established. Based on the fact that
FAF1
is a Fas-binding protein, we asked if
FAF1
interacted with other members of the Fas-death-inducing signaling complex (Fas-DISC) such as Fas-associated death domain protein (FADD) and
caspase-8
.
FAF1
could interact with
caspase-8
and FADD in vivo as well as in vitro. The death effector domains (DEDs) of
caspase-8
and FADD interacted with the amino acid 181-381 region of
FAF1
, previously known to have apoptotic potential. Considering that
FAF1
directly binds to Fas and
caspase-8
,
FAF1
shows similar protein-interacting characteristics to that of FADD. In the coimmunoprecipitation with an anti-Fas antibody (APO-1) in Jurkat cells, endogenous
FAF1
was associated with the precipitates in which
caspase-8
was present. By confocal microscopic analysis, both Fas and
FAF1
were detected in the cytoplasmic membrane before Fas activation, and in the cytoplasm after Fas activation. FADD and
caspase-8
colocalized with Fas in Jurkat cells validating the presence of
FAF1
in the authentic Fas-DISC. Overexpression of
FAF1
in Jurkat cells caused significant apoptotic death. In addition, the
FAF1
deletion mutant lacking the N terminus where Fas, FADD, and
caspase-8
interact protected Jurkat cells from Fas-induced apoptosis demonstrating dominant-negative phenotype. Cell death by overexpression of
FAF1
was suppressed significantly in both FADD- and
caspase-8
-deficient Jurkat cells when compared with that in their parental Jurkat cells. Collectively, our data show that
FAF1
is a member of Fas-DISC acting upstream of
caspase-8
.
...
PMID:Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex. 1270 23
Flavonoids are naturally occurring antioxidants, with several flavonoids shown to have chemopreventive effects on cancer. We investigated the effects of the flavonoid acacetin on human T cell leukemia Jurkat cells. Acacetin inhibited the proliferation of Jurkat cells by inducing apoptosis in a concentration- and time-dependent manner. Acacetin-induced cell death was characterized by changes in nuclear and cell morphology. Treatment of Jurkat cells with acacetin also induced caspase-3, -8 and -9 activities in a time-dependent manner. Acacetin-induced apoptosis was blocked by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor and a
caspase-8
inhibitor, but not by a caspase-9 inhibitor. In addition, acacetin promoted the expression of
FAF1
, phosphor-FADD, Apaf-1 and cytochrome c. Acacetin-induced apoptosis was also accompanied by upregulation of Bax, and downregulation of Bcl-2. Taken together, these results suggest that acacetin may induce apoptosis in T cell leukemia cells, possibly by activating the Fas-mediated pathway. These findings may help in designing cancer therapeutic and chemopreventive agents.
...
PMID:Acacetin induces apoptosis in human T cell leukemia Jurkat cells via activation of a caspase cascade. 2199 65
