DOI | Resolve DOI: https://doi.org/10.1139/o94-084 |
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Author | Search for: De Belle, I.; Search for: Testolin, L.; Search for: Pandey, S.; Search for: Carson, C.; Search for: Walker, P.; Search for: Armato, U.; Search for: Sikorska, Marianna |
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Format | Text, Article |
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Subject | apoptosis; thymocytes; proteolysis; transcription factors; gene expression |
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Abstract | Dexamethasone (Dex) accelerates the rate of apoptosis in thymocytes by a process thought to require gene expression. Among the genes implicated in the regulation of this phenomenon are the immediate early genes such as c-fos and c-jun, whose expression is modulated by a complement of preexisting transcription factors. We have analyzed the DNA-binding activity of these constitutive transcription factors during Dex-induced apoptosis in thymocytes to assess their functionality. We observed a progressive loss of the DNA-binding proteins in parallel with the appearance of the characteristic morphological and biochemical features of apoptosis. At the same time we have found a general increase in the nuclear proteolytic activity concomitant with a significant loss of the nuclear nonhistone chromosomal proteins. Indeed, cotreatment of thymocytes with the nonspecific serine protease inhibitor phenyl-methylsulphonyl fluoride was able to partially protect the stability of the DNA-binding proteins and alter the expression of the c-fos and c-jun genes but did not inhibit apoptosis. Our results suggest that the action of a protease(s) is responsible for the degradation of constitutive transcription factors during Dex-induced apoptosis, rendering the death pathway irreversible. |
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Publication date | 1994 |
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Publisher | National Research Council of Canada. NRC Research Press |
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In | |
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Language | English |
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Peer reviewed | Yes |
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NRC number | DEBELLE1994 |
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NPARC number | 9370071 |
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Export citation | Export as RIS |
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Report a correction | Report a correction (opens in a new tab) |
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Record identifier | be32af7b-8f2d-4f31-b185-9083c940d0f8 |
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Record created | 2009-07-10 |
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Record modified | 2022-12-19 |
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