Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells
Abstract
Death domain-associated protein (Daxx) is a multifunctional protein that modulates both cell death and transcription. Several recent studies have indicated that Daxx is a mediator of lymphocyte death and/or growth suppression, although the detailed mechanism is unclear. Previously, we reported that Daxx suppresses IL-6 family cytokine-induced gene expression by interacting with STAT3. STAT3 is important for the growth and survival of lymphocytes; therefore, we here examined the role of Daxx in the gp130/STAT3-dependent cell growth/survival signals. We found that Daxx suppresses the gp130/STAT3-dependent cell growth and that Daxx endogenously interacts with STAT3 and inhibits the DNA-binding activity of STAT3. Moreover, small-interfering RNA-mediated knockdown of Daxx enhanced the expression of STAT3-target genes and accelerated the STAT3-mediated cell cycle progression. In addition, knockdown of Daxx-attenuated lactate dehydrogenase leakage from cells, indicating that Daxx positively regulates cell death during gp130/STAT3-mediated cell proliferation. Notably, Daxx specifically suppressed the levels of Bcl2 mRNA and protein, even in cytokine-unstimulated cells, indicating that Daxx regulates Bcl2 expression independently of activated STAT3. These results suggest that Daxx suppresses gp130-mediated cell growth and survival by two independent mechanisms: inhibition of STAT3-induced transcription and down-regulation of Bcl2 expression.
Journal
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- European Journal of Immunology
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European Journal of Immunology 40 (12), 3570-3580, 2010-12
Wiley
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Keywords
Details 詳細情報について
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- CRID
- 1050001339007085184
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- NII Article ID
- 120002646892
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- HANDLE
- 2115/44384
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- ISSN
- 00142980
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles
- KAKEN