Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ectromelia virus (EV) virulence factor p28 (EVp28) is a member of a family of poxvirus proteins that are defined largely by the presence of a C-terminal RING finger motif and localization to virus factories within the cytoplasm of infected cells. Previously, overexpression of the Shope fibroma virus (SFV) homologue, N1R, in vaccinia virus (VV)-infected BGMK cells was found to inhibit virus-induced apoptosis. Here, we report that both EVp28 and overexpression of SFV N1R in poxvirus-infected HeLa cells protect specifically from UV light-induced apoptosis, but not from apoptosis induced by Fas or TNF. Further, we report that both VV and EV protect from apoptosis induced by UV, Fas and TNF. Immunoblot analysis indicates that EVp28 acts upstream of caspase-3, blocking activation of the protease in response to UV irradiation. Although no difference was found in replication of an EVp28(-) mutant virus, which expresses a truncated p28 protein lacking the RING motif, compared to EV wild-type in HeLa cells, UV irradiation of infected HeLa cells reduced the replication of the EV mutant compared with wild-type EV.
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PMID:Ectromelia virus virulence factor p28 acts upstream of caspase-3 in response to UV light-induced apoptosis. 1072 36

Tumorigenic leporipoxviruses encode catalytically inactive homologs of cellular Cu-Zn superoxide dismutase (SOD1). The function of the orthologous myxoma virus M131R and Shope fibroma virus S131R gene products is uncertain, but they inhibit SOD1 activity by a process linked to binding its copper chaperone. Using a superoxide-sensitive dye (hydroethidine), we observed that virus infection increased intracellular superoxide levels in an M/S131R-dependent manner. To see whether this effect promotes infection, we deleted the Shope fibroma virus S131R gene and compared the clinical manifestations of wild-type and mutant virus infections in rabbits. S131RDelta virus produced significantly smaller fibroxanthosarcoma-like growths in vivo and, at a point where these growths were already receding, wild-type infections still showed extensive leukocyte infiltration, necrosis, and fibromatous cell proliferation. Coincidentally, whereas Jurkat cells are protected from mitochondria- and Fas-mediated apoptosis by wild-type myxoma virus in vitro, M131RDelta virus could not block Fas-initiated apoptosis as judged by DNA laddering, terminal deoxynucleotidyltransferase-mediated dUTP-fluorescein nick end labeling, and caspase 3 cleavage assays. These data suggest that tumorigenic poxviruses can modulate intracellular redox status to their advantage to stimulate infected cell growth and inhibit programmed cell death.
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PMID:Tumorigenic poxviruses up-regulate intracellular superoxide to inhibit apoptosis and promote cell proliferation. 1582 94