A Functional Role for Death Proteases in s-Myc- and c-Myc-Mediated Apoptosis

Implication of c-Myc in apoptosis induced by the retinoid CD437 in human lung carcinoma cells

“…Of the ten known caspases, caspase-3 or CPP32 is one of the strongest candidates for being a mammalian cell death-inducing protease that cleaves PARP and other vital proteins (Patel et al, 1996;Martin and Green, 1995b). Recently, it has been suggested that CPP32-like caspase plays a critical role in c-Myc-mediated apoptosis (Kagaya et al, 1997;Kangas et al, 1998). Our previous study (Sun et al, 1999) showed that the caspase inhibitors Z-DEVD FMK and Z-VAD FMK could block not only CD437-induced CPP32-like caspase activation but also CD437-induced apoptosis in H1792 and H460 cells.…”

“…Recently, the important role of caspases, especially caspase-3 or CPP32, in c-Myc-mediated apoptosis has been highlighted (Kagaya et al, 1997;Kangas et al, 1998). CD437 induced CPP32-like caspase activation (Figure 5a), which was accompanied by increased DNA fragmentation (Figure 5b).…”

“…CPP32-like caspase activity was measured as described previously (Kagaya et al, 1997). Brie¯y, cells were collected and lysed for 20 min on ice in lysis bu er containing 10 mM HEPES-KOH (pH 7.4), 2 mM EDTA, 0.1% 3-[(3-cholamidopropyl) dimethyl-ammonio ] -1 -propanesulfonats (CHAPS), 1 mM PMSF, and 5 mM DTT.…”

Cleavage of epidermal growth factor receptor by caspase during apoptosis is independent of its internalization

“…It appears that metalloproteases, cathepsin/palpain, and other cysteine proteases are not involved in EGFR downregulation. The protective effect of AEBSF may be due to its antiapoptotic effect on cells (Kagaya et al, 1997;Park et al, 2000). However, the possible involvement of AEBSF-sensitive proteases remains an open question.…”

Mechanisms of apoptosis by c-Myc

“…A rudimentary genetic analysis performed using a canonical set of cMyc deletion mutants (Stone et al, 1987) indicated overlap in the terminal regions of c-Myc required for apoptosis or transformation, illustrating crucial requirements for the Myc Box-containing NTD and the b/ HLH/LZ-containing CTD . Cell death by c-Myc in the Rat1 system was subsequently shown to be associated with the activation of certain Jun kinases (Jnks) and caspase-3 (Kagaya et al, 1997;Yu et al, 1997;Kangas et al, 1998), which is crucial to produce the associated chromatin collapse and nucleosomal DNA degradation. c-Myc is also responsible for cell death in Burkitt's lymphoma cells and EBVimmortalized B cells deprived of autocrine factors (Milner et al, 1993;Cherney et al, 1994).…”