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)
Apoptosis and autophagy are distinct cellular processes that can be highly interconnected. The cross talk between the two processes is indispensable in determining the overall cell fate. Although the apoptosis-promoting effect of caspases has been demonstrated, the roles of autophagy-related proteins and even autophagy itself in regulating apoptosis remain poorly understood. In our present study, we found that downregulation of ubiquitin E3 ligase
ASB3
led to enhanced mitochondrial apoptosis as well as autophagy, which synergistically promoted cell death in hepatocellular carcinoma (HCC). We observed the activation of
caspase-8
and decrease of autophagy protein Beclin1 in apoptotic cells that were depleted of
ASB3
. Beclin1 was mainly cleaved by activated
caspase-8
and active Beclin1 initiated mitochondrial apoptosis via locating its C-terminal fragment to mitochondria. In addition, knocking down of Beclin1 markedly blocked the apoptosis, indicating its essential role in the process. Notably, our study indicated that enhanced autophagy level might be involved in the activation of
caspase-8
and promote the apoptosis. Taken together, our results demonstrated that
ASB3
can regulate mitochondrial pathway of apoptosis by controlling
caspase-8
mediated cleavage of Beclin1 in HCC. Therefore,
ASB3
may potentially serve as a novel target for HCC therapy, especially when combined with autophagy agonist.
...
PMID:ASB3 knockdown promotes mitochondrial apoptosis via activating the interdependent cleavage of Beclin1 and caspase-8 in hepatocellular carcinoma. 3101 35
