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:3.4.22.36 (
caspase-1
)
6,285
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cyclin A1 is an A-type cyclin that directly binds to CDK2 to regulate cell-cycle progression. In the present study, we found that doxorubicin decreased the expression of
cyclin A1
at the protein level in A549 lung cancer cells, while markedly downregulating its mRNA levels. Interestingly, doxorubicin upregulated
caspase-1
in a concentration-dependent manner, and z-YAVD-fmk, a specific inhibitor of
caspase-1
, reversed the doxorubicin-induced decrease in
cyclin A1
in A549 lung cancer and MCF7 breast cancer cells. Active
caspase-1
effectively cleaved
cyclin A1
at D165 into two fragments, which in vitro cleavage assays showed were further cleaved by caspase-3. Finally, we found that overexpression of
cyclin A1
significantly reduced the cytotoxicity of doxorubicin, and knockdown of
cyclin A1
by RNA interference enhanced the sensitivity of cells to ionizing radiation. Our data suggest a new mechanism for the downregulation of
cyclin A1
by DNA-damaging stimuli that could be intimately involved in the cell death induced by DNA damage-inducing stimuli, including doxorubicin and ionizing radiation.
...
PMID:Implications of caspase-dependent proteolytic cleavage of cyclin A1 in DNA damage-induced cell death. 2528 37
