期刊
PLOS ONE
卷 8, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0061085
关键词
-
资金
- New York State Peter T. Rowley Breast Cancer Research Award [C026592]
Unlike other caspases, caspase-2 appears to be a nuclear protein although immunocytochemical studies have suggested that it may also be localized to the cytosol and golgi. Where and how caspase-2 is activated in response to apoptotic signals is not clear. Earlier immunocytochemistry studies suggest that caspase-2 is activated in the nucleus and through cleavage of BID leads to increased mitochondrial permeability. More recent studies using bimolecular fluorescence complementation found that caspase-2 oligomerization that leads to activation only occurs in the cytoplasm. Thus, apoptotic signals may lead to activation of caspase-2 which may already reside in the cytoplasm or lead to release of nuclear caspase-2 to the extranuclear cytoplasmic compartment. It has not been possible to study release of nuclear caspase-2 to the cytoplasm by cell fractionation studies since cell lysis is known to release nuclear caspase-2 to the extra-nuclear fraction. This is similar to what is known about unliganded nuclear estrogen receptor-alpha (ER alpha) when cells are disrupted. In this study we found that pretreatment of cells with N-ethylmaleimide (NEM), which alkylates cysteine thiol groups in proteins, completely prevents redistribution of caspase-2 and ER alpha from the nucleus to the extra-nuclear fraction when cells are lysed. Using this approach we provide evidence that apoptotic signals rapidly leads to a shift of caspase-2 from the nucleus to the extra-nuclear fraction, which precedes the detection of apoptosis. These findings are consistent with a model where apoptotic signals lead to a rapid shift of caspase-2 from the nucleus to the cytoplasm where activation occurs.
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