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:3.4.22.56 (
caspase-3
)
35,750
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The nuclear factor Acinus has been suggested to mediate apoptotic chromatin condensation after caspase cleavage. However, this role has been challenged by recent observations suggesting a contribution of Acinus in apoptotic internucleosomal DNA cleavage. We report here that
AAC-11
, a survival protein whose expression prevents apoptosis that occurs on deprivation of growth factors, physiologically binds to Acinus and prevents Acinus-mediated DNA fragmentation.
AAC-11
was able to protect Acinus from
caspase-3
cleavage in vivo and in vitro, thus interfering with its biological function. Interestingly,
AAC-11
depletion markedly increased cellular sensitivity to anticancer drugs, whereas its expression interfered with drug-induced cell death.
AAC-11
possesses a leucine-zipper domain that dictates, upon oligomerization, its interaction with Acinus as well as the antiapoptotic effect of
AAC-11
on drug-induced cell death. A cell permeable peptide that mimics the leucine-zipper subdomain of
AAC-11
, thus preventing its oligomerization, inhibited the
AAC-11
-Acinus complex formation and potentiated drug-mediated apoptosis in cancer cells. Our results, therefore, show that targeting
AAC-11
might be a potent strategy for cancer treatment by sensitization of tumour cells to chemotherapeutic drugs.
...
PMID:The antiapoptotic protein AAC-11 interacts with and regulates Acinus-mediated DNA fragmentation. 1938 94
