Previous Article | Next Article 
Molecular and Cellular Biology, August 2005, p. 7344-7356, Vol. 25, No. 16
0270-7306/05/$08.00+0 doi:10.1128/MCB.25.16.7344-7356.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Identification of a Crucial Site for Synoviolin Expression
Kaneyuki Tsuchimochi,1,2 Naoko Yagishita,1 Satoshi Yamasaki,1 Tetsuya Amano,1 Yukihiro Kato,1 Ko-ichi Kawahara,3 Satoko Aratani,1 Hidetoshi Fujita,1 Fengyun Ji,1 Akiko Sugiura,1 Toshihiko Izumi,1,2 Asako Sugamiya,1 Ikuro Maruyama,3 Akiyoshi Fukamizu,4 Setsuro Komiya,2 Kusuki Nishioka,1 and Toshihiro Nakajima1*Department of Genome Science, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa 216-8512,1 Departments of Orthopedic Surgery,2 Laboratory and Molecular Medicine, Kagoshima Graduate School of Medical and Dental Sciences, Kagoshima 890-8520,3 Institute of Applied Biochemistry and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan4
Received 5 December 2004/ Returned for modification 16 January 2005/ Accepted 18 May 2005
Synoviolin is an E3 ubiquitin ligase localized in the endoplasmic reticulum (ER) and serving as ER-associated degradation system. Analysis of transgenic mice suggested that synoviolin gene dosage is implicated in the pathogenesis of arthropathy. Complete deficiency of synoviolin is fatal embryonically. Thus, alternation of Synoviolin could cause breakdown of ER homeostasis and consequently lead to disturbance of cellular homeostasis. Hence, the expression level of Synoviolin appears to be important for its biological role in cellular homeostasis under physiological and pathological conditions. To examine the control of protein level, we performed promoter analysis to determine transcriptional regulation. Here we characterize the role of synoviolin transcription in cellular homeostasis. The Ets binding site (EBS), termed EBS-1, from position –76 to –69 of the proximal promoter, is responsible for synoviolin expression in vivo and in vitro. Interestingly, transfer of EBS-1 decoy into NIH 3T3 cells conferred not only the repression of synoviolin gene expression but also a decrease in cell number. Fluorescence-activated cell sorter analysis using annexin V staining confirmed the induction of apoptosis by EBS-1 decoy and demonstrated recovery of apoptosis by overexpression of Synoviolin. Our results suggest that transcriptional regulation of synoviolin via EBS-1 plays an important role in cellular homeostasis. Our study provides novel insight into the transcriptional regulation for cellular homeostasis.
* Corresponding author. Mailing address: Department of Genomic Science, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki, Kanagawa 216-8512, Japan. Phone: 81-44-977-8111, ext. 4113. Fax: 81-44-977-9772. E-mail: nakashit{at}marianna-u.ac.jp.
Molecular and Cellular Biology, August 2005, p. 7344-7356, Vol. 25, No. 16
0022-538X/05/$08.00+0 doi:10.1128/MCB.25.16.7344-7356.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Krieg, A. J., Hammond, E. M., Giaccia, A. J.
(2006). Functional Analysis of p53 Binding under Differential Stresses.. Mol. Cell. Biol.
26: 7030-7045
[Abstract] [Full Text] -
Nakamura, N., Shimaoka, Y., Tougan, T., Onda, H., Okuzaki, D., Zhao, H., Fujimori, A., Yabuta, N., Nagamori, I., Tanigawa, A., Sato, J., Oda, T., Hayashida, K., Suzuki, R., Yukioka, M., Nojima, H., Ochi, T.
(2006). Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients.. DNA Res
13: 169-183
[Abstract] [Full Text]
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»