Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ribosome-inactivating stresses possess a potent regulatory activity against tumor cell progression. In this study, we demonstrated that macrophage inhibitory cytokine-1 (MIC-1) and its associated signals determined the colon cancer cell response to the chemical ribotoxic stress. The ribotoxic stress agent anisomycin-induced MIC-1 gene expression which was involved in the ribotoxin-induced apoptotic pathway. MIC-1 was also a critical inducer of apoptosis-related gene products such as activated urokine-type plasminogen activator (PLAU) and PLAU receptor (uPAR). When MIC-1 or PLAU action was repressed in the tumor cells, the chemical ribotoxic stress triggered a survival-related MAP kinase such as ERK. Mechanistically, gene expression of apoptosis-mediator MIC-1 was enhanced by activating transcription factor 3 (ATF-3) via the p38 MAP kinase signaling pathway. Moreover, both promoter activity and mRNA stability of MIC-1 gene were up-regulated by ribotoxic anisomycin via the p38 MAP kinase signaling pathway. In conclusion, ribotoxic anisomycin-induced MIC-1 expression via p38-ATF3 pathway and subsequent apoptosis while suppressing survival ERK signal in the colon cancer cells. The results of this study provide mechanistic insight into tumor cell decision for death or survival pathways in response to ribosome-disrupting stresses from chemotherapeutics.
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PMID:Macrophage inhibitory cytokine-1 (MIC-1) and subsequent urokinase-type plasminogen activator mediate cell death responses by ribotoxic anisomycin in HCT-116 colon cancer cells. 1954 Feb 5

The release of the serine proteinase tissue-type plasminogen activator (tPA) from cerebral cortical neurons has a neuroprotective effect in the ischemic brain. Because excitotoxicity is a basic mechanism of ischemia-induced cell death, here we investigated the effect of tPA on excitotoxin-induced neuronal death. We report that genetic overexpression of neuronal tPA or treatment with recombinant tPA renders neurons resistant to the harmful effects of an excitotoxic injury in vitro and in vivo. We found that at concentrations found in the ischemic brain, tPA interacts with synaptic but not extrasynaptic NMDARs. This effect is independent of tPA's proteolytic properties and leads to a rapid and transient phosphorylation of the extracellular signal regulated kinases1/2 (ERK1/2), with ERK1/2-mediated activation of the cAMP response element binding protein (CREB) and induction of the neuroprotective CREB-regulated activating transcription factor 3 (Atf3). In line with these observations, Atf3 down-regulation abrogates the protective effect of tPA against excitotoxin-induced neuronal death. Our data indicate that tPA preferentially activates synaptic NMDARs via a plasminogen-independent mechanism turning on a cell signaling pathway that protects neurons from the deleterious effects of excitotoxicity.
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PMID:Tissue-type plasminogen activator protects neurons from excitotoxin-induced cell death via activation of the ERK1/2-CREB-ATF3 signaling pathway. 2306 1