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)

Co-chaperone p23 is a component of the heat-shock protein (Hsp)90 multiprotein-complex and is an important modulator of Hsp90 activity. Hsp90 client proteins involved in oncogenic survival signaling are frequently mutated in leukemia, and the integrity of the Hsp90 complex could therefore be important for leukemic cell survival. We demonstrate here that p23 is cleaved to a stable 17 kDa fragment in leukemic cell lines treated with commonly used chemotherapeutic drugs. The cleavage of p23 paralleled the activation of procaspase-7 and -3 and was suppressed by the caspase-3/-7 inhibitor DEVD-FMK. In vitro translated 35S-p23 (in reticulocyte lysate) was cleaved at D142 and D145 by caspase-7 and -3. Cleavage of p23 occurred in caspase-3-deficient MCF-7 cells, suggesting a role for caspase-7 in intact cells. The Hsp90 inhibitor geldanamycin enhanced caspase-dependent p23 cleavage both in vitro and in intact cells. Geldanamycin also enhanced anthracycline-induced caspase activation and apoptosis. We conclude that p23 is a prominent target in leukemic cell apoptosis. Geldanamycin enhanced p23 cleavage both by rendering p23 more susceptible to caspases and by enhancing chemotherapy-induced caspase activation. These findings underscore the importance of the Hsp90-complex in antileukemic treatment, and suggest that p23 may have a role in survival signaling.
Leukemia 2004 Dec
PMID:Caspase-dependent, geldanamycin-enhanced cleavage of co-chaperone p23 in leukemic apoptosis. 1548 79

To investigate apoptosis of mouse leukemia cell (WEHI-3) induced by econazole and its mechanism, apoptosis induced by econazole was examined by flow cytometry, while free calcium ([Ca(2+)]i) was determined by Fura-2 fluorescein load technique. The protein was isolated from endoplasmic reticulum of WEHI-3 cells, and then the expression of caspase-12 and caspase-7 was evaluated by Western blot. The results showed that WEHI-3 exhibited typical change of apoptosis when it was treated by econazole, [Ca(2+)]i was significantly higher in comparison with the control. The expression of caspase-12 and caspase-7 enhanced as the econazole concentration increased. In conclusion, econazole can induce WEHI-3 cell apoptosis and the caspase-12 plays a key role in this process.
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PMID:[Experimental study on apoptosis in leukemia cells induced by econazole]. 1597 27