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

Muromoto, Ryuta; Kuroda, Makoto; Togi, Sumihito; Sekine, Yuichi; Nanbo, Asuka; Shimoda, Kazuya; Oritani, Kenji; Matsuda, Tadashi

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

Muromoto, Ryuta; Kuroda, Makoto; Togi, Sumihito et al.

European Journal of Immunology, 2010, 40(12), 3570-3580

Permalink : https://hdl.handle.net/2115/44384

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アクセス権	open access
URI	https://hdl.handle.net/2115/44384
タイトル	Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells
著者	Muromoto, Ryuta ; Kuroda, Makoto ; Togi, Sumihito ; Sekine, Yuichi ; Nanbo, Asuka ; Shimoda, Kazuya ; Oritani, Kenji ; Matsuda, Tadashi
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
著者名 Kuroda, Makoto
著者名 Togi, Sumihito
e-Rad_Researcher 20396295 著者名 Sekine, Yuichi
e-Rad_Researcher 60359487 著者名 Nanbo, Asuka
e-Rad_Researcher 90311844 著者名 Shimoda, Kazuya
e-Rad_Researcher 70324762 著者名 Oritani, Kenji
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
キーワード	Cell death
	Daxx
	gp130
	IL-6
	STAT3
発行日	2010-12
出版者	Wiley
収録物名	European Journal of Immunology
巻(号)	40(12)
ページ	3570-3580
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is the pre-peer-reviewed version of the following article: FULL CITE, which has been published in final form at http://hdl.handle.net/10.1002/eji.201040688
PISSN	0014-2980
関連情報	PMID 21108476
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1002/eji.201040688