Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The s-Myc is similar to c-Myc in its ability to induce apoptosis requiring caspase activation. However, s-Myc is distinct from c-Myc in that it has activity to suppress tumor growth and does not require wild-type p53 to induce apoptosis. These facts suggest differential regulation between s-Myc and c-Myc. Here we showed that s-Myc-mediated apoptosis triggered by UV was not inhibited by the inactive form mutant JNK (APF), though c-Myc-mediated apoptosis was. Moreover, we found that JNK did not affect the transactivation activity of s-Myc, but stimulated that of c-Myc. In contrast, both Myc-mediated apoptosis and caspase-3-like protease activation were suppressed by kinase-negative MKK6 and an inactive form mutant p38(AGF). Our results indicate that s-Myc does not require the JNK signaling unlike c-Myc during UV-triggered apoptosis, but the MKK6/p38MAPK pathway might regulate common apoptotic machinery for both s-Myc and c-Myc upstream of caspase.
 ...
PMID:Differential role of the JNK and p38 MAPK pathway in c-Myc- and s-Myc-mediated apoptosis. 1062 2

Vascular smooth muscle cell (VSMC) apoptosis accelerates atherosclerosis and promotes restenosis following vascular injury. The current study examined the effects of cellular repressor of E1A-stimulated genes (CREG), a novel glycoprotein inhibiting transcription activation, on the regulation of VSMC apoptosis. Serum starvation or treatment of human VSMCs with apoptosis inducers (STS or VP-16) significantly reduced CREG expression and caused caspase-3 activation. CREG downregulation and caspase-3 activation were inversely related, suggesting that reduced CREG expression may contribute to VSMC apoptosis. Both loss-of-function (CREG-DW produced by retroviruses expressing CREG shRNAs) and gain-of-function (CREG-UP produced by retroviral infection with vector pLNCX-CREG) studies were performed to confirm this hypothesis. CREG-DW significantly increased VSMC apoptosis, whereas CREG-UP significantly reduced apoptosis. Moreover, p38 and JNK mitogen-activated protein kinases were significantly upregulated in CREG-DW and significantly reduced in CREG-UP VSMCs. More importantly, CREG-DW-induced VSMC apoptosis was blocked by the p38-specific inhibitor SB203580 or by overexpression of a dominant-negative P38 alpha (p38 alpha AGF). Balloon injury-induced vascular caspase-3 activation was significantly inhibited by treatment with recombinant CREG protein. These results demonstrated for the first time that CREG plays a key role in modulating VSMC apoptosis through the p38 and JNK signal transduction pathways, both in vitro and in situ.
 ...
PMID:Cellular repressor of E1A-stimulated genes inhibits human vascular smooth muscle cell apoptosis via blocking P38/JNK MAP kinase activation. 2006 3