Cleavage of cten by caspase-3 during apoptosis.
Normal endothelial and epithelial cells undergo apoptosis when cell adhesion and spreading are disrupted, implying a critical role of focal adhesions in cell survival. Cten is a focal adhesion molecule of the tensin family. In contrast to other tensins, cten expression is limited to very few tissues, such as the prostate, and only in epithelial cells. Here, we have explored the potential roles of cten in apoptosis. We found cten was cleaved during apoptosis induced by staurosporine in normal prostate epithelial cells. By using recombinant caspases and site-directed mutagenesis, we have identified caspase-3 as the major protease to digest cten at the DSTD(570 downward arrow)S site. The biological relevance of cten-cleaved fragments was demonstrated by cells ectopically expressing these fragments. Cten fragment (residues 571-715) containing the phosphotyrosine-binding domain significantly reduced the growth rate. Detection of cleaved poly(ADP-ribose) polymerase and annexin binding in cells expressing cten (571-715) indicated that a fraction of cells underwent apoptosis. These results demonstrate that cten is a target of caspase-3 and the resultant fragments could further promote apoptosis.
Lo
Su-Shun
SS
Division of General Surgery, Taipei-Veterans General Hospital, National Yang Ming University, Taipei, Taiwan.
Lo
Su Huey
SH
Lo
Su Hao
SH
D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000494:pharmacology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018929:Cell Culture Techniques; D002470:Cell Survival; D004847:Epithelial Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins; D016297:Mutagenesis, Site-Directed; D011467:Prostate / Q000166:cytology; D000070876:Tensins
D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C000603371:TNS4 protein, human; D000070876:Tensins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases