Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells
Title: | Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells |
Authors: | Muromoto, Ryuta Browse this author →KAKEN DB | Kuroda, Makoto Browse this author | Togi, Sumihito Browse this author | Sekine, Yuichi Browse this author →KAKEN DB | Nanbo, Asuka Browse this author →KAKEN DB | Shimoda, Kazuya Browse this author →KAKEN DB | Oritani, Kenji Browse this author →KAKEN DB | Matsuda, Tadashi Browse this author →KAKEN DB |
Keywords: | Cell death | Daxx | gp130 | IL-6 | STAT3 |
Issue Date: | Dec-2010 |
Publisher: | Wiley |
Journal Title: | European Journal of Immunology |
Volume: | 40 |
Issue: | 12 |
Start Page: | 3570 |
End Page: | 3580 |
Publisher DOI: | 10.1002/eji.201040688 |
PMID: | 21108476 |
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. |
Rights: | 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 |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/44384 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 松田 正
|