Caspase-mediated cleavage of cytoskeletal actin plays a positive role in the process of morphological apoptosis.
Tumors result from the imbalance between cell growth and apoptosis. One of the characteristic changes in cancers is the abnormality in cytoskeleton, which suggests some roles of cytoskeletal proteins in tumorigenesis or the maintenance of tumor cells. Previously we showed that cytoskeletal actin is the substrate of caspases, the proteases responsible for apoptosis, while the role of actin cleavage in apoptosis remained unknown. To examine the cleavage of actin in vivo, we extensively performed immunoblot analysis using actin fragment-specific antibody. Here, we showed that, in some solid tumor cells, induction of apoptosis was accompanied by caspase-dependent actin-cleavage to 15 and 31 kDa fragments in vivo. To elucidate the role of actin-cleavage further, we introduced actin cleaved-fragments. We found that ectopic expression of an actin 15 kDa fragment induces morphological changes resembling those of apoptotic cells. The expression of the actin fragment induced a dramatic change of cellular actin localization, as visualized by enhanced green fluorescent protein (EGFP)-tagged actin, while the actin fragment expression did not cause caspase activation nor the cleavage of a marker substrate protein, poly (ADP-ribose) polymerase. These results indicate that actin cleavage could play a positive role in the morphological changes of apoptosis downstream of caspase activation.
Mashima
T
T
Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Naito
M
M
Tsuruo
T
T
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000199:Actins; D010446:Peptide Fragments; D020169:Caspases