Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptotic proteases cleave and inactivate survival signaling molecules such as Akt/PKB, phospholipase C (PLC)-gamma1, and Bcl-2. We have found that treatment of A431 cells with tumor necrosis factor-alpha in the presence of cycloheximide resulted in the cleavage of epidermal growth factor receptor (EGFR) as well as the activation of caspase-3. Among various caspases, caspase-1, caspase-3 and caspase-7 were most potent in the cleavage of EGFR in vitro. Proteolytic cleavage of EGFR was inhibited by both YVAD-cmk and DEVD-fmk in vitro. We also investigated the effect of caspase-dependent cleavage of EGFR upon the mediation of signals to downstream signaling molecules such as PLC-gamma1. Cleavage of EGFR by caspase-3 significantly impaired the tyrosine phosphorylation of PLC-gamma1 in vitro. Given these results, we suggest that apoptotic protease specifically cleaves and inactivates EGFR, which plays crucial roles in anti-apoptotic signaling, to abrogate the activation of EGFR-dependent downstream survival signaling molecules.
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PMID:Proteolytic cleavage of epidermal growth factor receptor by caspases. 1122 7

We have investigated the mechanism of IL-7-mediated inhibition of dexamethasone-induced apoptosis in T cells. Broad-spectrum caspase inhibitors block dexamethasone-triggered nuclear fragmentation, but not the loss of mitochondrial transmembrane potential or membrane integrity in CD3(+) mature T cells isolated from adult mouse spleens. IL-7 blocked dexamethasone-induced apoptosis and the processing of caspase-3 and caspase-7. IL-7 also blocked dexamethasone-triggered dephosphorylation of the serine-threonine kinase Akt/PKB and its target, the Ser(136) residue in Bad. The loss of anti-apoptotic proteins Bcl-x(L) and inhibitor of apoptosis protein-2 (IAP-2) was also blocked by IL-7. The protective effect was attenuated by pharmacological inhibitors of phosphatidylinositol-3 kinase (PI3K) with one exception: inhibition of PI3K did not abrogate Bcl-x(L) expression in the presence of IL-7. The anti-apoptotic role of Akt suggested by these experiments was tested by overexpression of constitutively active Akt, which blocked dexamethasone-induced apoptosis and elevated IAP-2 but not Bcl-x(L) levels in a mature T cell line. Thus, IL-7 regulates IAP-2 expression and inhibits dexamethasone-induced apoptosis by activating Akt via PI3K-dependent signaling, but regulates Bcl-x(L)expression via a PI3K-independent pathway in mature T cells.
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PMID:IL-7 inhibits dexamethasone-induced apoptosis via Akt/PKB in mature, peripheral T cells. 1267 57

The present study explored the effect of telomerase reverse transcriptase (TERT) on the growth and apoptosis of fibrosarcoma, and investigated the potential molecular signalling pathways underlying its effect. A plasmid was constructed in order to overexpress TERT and siRNA was used to knockdown TERT. The effect of TERT on fibrosarcoma cells in vitro was studied by performing reverse transcription-quantitative PCR and western blotting to determine the expression of p53, survivin, caspase-3, caspase-7 and PKB. Knockdown of TERT suppressed cell growth, decreased fibrosarcoma volume, decreased survivin and PKB expression, and increased caspase-3 expression. The results of the present study suggest that TERT regulates the growth of fibrosarcoma in vitro and in vivo, and that this is associated with the expression of caspase-3 and survivin, in addition to the PKB signalling pathway.
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PMID:Effect of TERT on the growth of fibrosarcoma via caspase-3, survivin and PKB. 2878 28