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Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells

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Title: Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells
Authors: Muromoto, Ryuta Browse this author
Kuroda, Makoto Browse this author
Togi, Sumihito Browse this author
Sekine, Yuichi Browse this author
Nanbo, Asuka Browse this author
Shimoda, Kazuya Browse this author
Oritani, Kenji Browse this author
Matsuda, Tadashi Browse this author
Keywords: Cell death
Issue Date: Dec-2010
Journal Title: European Journal of Immunology
Volume: 40
Issue: 12
Start Page: 3570
End Page: 3580
Publisher DOI: 10.1002/eji.201040688
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.
Type: article (author version)
Appears in Collections:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正


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