Abstract
Overexpression of TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis. In this study, we found that TIEG1 was significantly up-regulated during apoptosis induced by homoharringtonine or velcade. Overexpression of TIEG1 could induce apoptosis in K562 cells and promote apoptosis induced by HHT or velcade. TIEG1-induced apoptosis was shown to involve Bax and Bim up-regulation, Bcl-2 and Bcl-XL down-regulation, release of cytochrome c from mitochondria into the cytosol, activation of caspase 3 and disruption of the mitochondrial membrane potential (DeltaPsim). We concluded that TIEG1 is a key regulator which induces and promotes apoptosis through the mitochondrial apoptotic pathway.
MeSH terms
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Animals
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Apoptosis / drug effects*
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Boronic Acids / toxicity*
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Bortezomib
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DNA-Binding Proteins / metabolism*
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Early Growth Response Transcription Factors / metabolism*
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Neoplastic
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Harringtonines / toxicity*
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Homoharringtonine
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Humans
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K562 Cells
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Kruppel-Like Transcription Factors / metabolism*
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Melanoma, Experimental / metabolism
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Melanoma, Experimental / pathology
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Mice
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Mitochondria / metabolism*
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Pyrazines / toxicity*
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Transcription Factors / metabolism*
Substances
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Boronic Acids
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DNA-Binding Proteins
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Early Growth Response Transcription Factors
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Harringtonines
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KLF10 protein, human
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Kruppel-Like Transcription Factors
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Pyrazines
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Tieg1 protein, mouse
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Transcription Factors
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Bortezomib
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Homoharringtonine