Actin cleavage in various tumor cells is not a critical requirement for executing apoptosis.
Actin is a major cytoskeletal protein which is involved in many physiological cellular functions such as motility, cell shape, and adhesion. Recently, actin has also been reported to be cleaved by apoptotic proteases (i.e., caspases) and this cleavage is thought to contribute to the apoptotic process. However, conflicting data also exists as to whether actin represents a true caspase substrate during apoptosis induction in vivo (i.e., inside the cells). In this study, we critically examined the actin cleavage patterns during apoptosis of several tumor cell lines derived from three different species (i.e., mouse, rat, and human). Our findings demonstrate that: 1) actin cleavage in vivo is not a common phenomenon since apoptosis caused by multiple inducers in most cell types examined occurs without evidence of actin degradation; and 2) in certain cell types (e.g., U937), spontaneous, actin cleavage is observed which is not prevented by various specific chemical/peptide inhibitors of proteases such as caspases or serine proteases although apoptosis per se is retarded by some of these inhibitors. Our results conclude that actin is not a critical substrate for apoptotic proteases in vivo during apoptosis.
Rice
R L
RL
Wayne State University, Department of Biological Sciences, Detroit, USA.
Tang
D G
DG
Taylor
J D
JD
D000199:Actins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002279:Carcinoma 256, Walker / Q000378:metabolism / Q000473:pathology; D016895:Culture Media, Serum-Free; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D000199:Actins; D016895:Culture Media, Serum-Free; D011480:Protease Inhibitors