HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 48, 36683-36690, December 1, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/48/36683    most recent M607374200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, Y. Articles by Takaesu, G. Search for Related Content PubMed PubMed Citation Articles by Lu, Y. Articles by Takaesu, G. Social Bookmarking                      What's this?

Loss of SOCS3 Gene Expression Converts STAT3 Function from Anti-apoptotic to Pro-apoptotic^*

From the Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

The transcription factor STAT3 is activated by interleukin-6-related cytokines and has been implicated as an oncogene; it promotes cell proliferation and is anti-apoptotic. However, in some cases, STAT3 has been shown to be pro-apoptotic, especially in mammary epithelial cells. In this report, we generated SOCS3-deficient murine embryonic fibroblasts (MEFs), in which STAT3 activation is extremely enhanced and prolonged. We found that LIF induces caspase-3 activation and apoptosis of SOCS3^–/– MEFs. Exogenous expression of the dominant negative form of STAT3 but not STAT1 suppressed LIF-induced apoptosis of SOCS3^–/– MEFs, indicating that STAT3 plays a critical role in apoptosis induction. As shown in mammary gland epithelial cells, expression of the phosphatidylinositol 3-kinase regulatory subunits p50 and p55 was induced in response to LIF in SOCS3^–/– MEFs but not in wild-type MEFs, and Akt/protein kinase B activity was substantially reduced in SOCS3^–/– MEFs. Furthermore, we found that some of the STAT3 target genes related to apoptosis and proliferation, such as Bcl-2 and cyclin D1, were repressed upon LIF treatment in SOCS3^–/– cells. Not only the up-regulation of p50 and p55 but also the repression of cyclin D1 and Bcl-2 in SOCS3^–/– MEFs was inhibited by dominant negative STAT3. These data suggest that prolonged activation of STAT3 could induce apoptosis/growth arrest rather than anti-apoptosis and proliferation in certain cases, and SOCS3 is a critical regulator of this balance.

Received for publication, August 3, 2006 , and in revised form, October 6, 2006.

^* This work was supported by special grants-in-aid from the Ministry of Education, Science Technology, Sports, and Culture of Japan; the Haraguchi Memorial Foundation; the Yamanouchi Foundation for Research on Metabolic Disorders; the Takeda Science Foundation; the Mochida Memorial Foundation; the Kato Memorial Foundation; and the Uehara Memorial Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-92-642-6822; Fax: 81-92-642-6825; E-mail: takaesug{at}bioreg.kyushu-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Shiraishi, H. Yoshida, K. Saeki, Y. Miura, S. Watanabe, T. Ishizaki, M. Hashimoto, G. Takaesu, T. Kobayashi, and A. Yoshimura Prostaglandin E2 is a major soluble factor produced by stromal cells for preventing inflammatory cytokine production from dendritic cells Int. Immunol., September 1, 2008; 20(9): 1219 - 1229. [Abstract] [Full Text] [PDF]

				X. Liu, M. G. Mameza, Y. S. Lee, C. I. Eseonu, C.-R. Yu, J. J. Kang Derwent, and C. E. Egwuagu Suppressors of Cytokine-Signaling Proteins Induce Insulin Resistance in the Retina and Promote Survival of Retinal Cells Diabetes, June 1, 2008; 57(6): 1651 - 1658. [Abstract] [Full Text] [PDF]

				K. Tanaka, K. Ichiyama, M. Hashimoto, H. Yoshida, T. Takimoto, G. Takaesu, T. Torisu, T. Hanada, H. Yasukawa, S. Fukuyama, et al. Loss of Suppressor of Cytokine Signaling 1 in Helper T Cells Leads to Defective Th17 Differentiation by Enhancing Antagonistic Effects of IFN-{gamma} on STAT3 and Smads J. Immunol., March 15, 2008; 180(6): 3746 - 3756. [Abstract] [Full Text] [PDF]

				Y. Bai, U. Ahmad, Y. Wang, J. H. Li, J. C. Choy, R. W. Kim, N. Kirkiles-Smith, S. E. Maher, J. G. Karras, C. F. Bennett, et al. Interferon-{gamma} Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation J. Biol. Chem., March 14, 2008; 283(11): 6832 - 6842. [Abstract] [Full Text] [PDF]

				G. Gausdal, B. T. Gjertsen, E. McCormack, P. Van Damme, R. Hovland, C. Krakstad, O. Bruserud, K. Gevaert, J. Vandekerckhove, and S. O. Doskeland Abolition of stress-induced protein synthesis sensitizes leukemia cells to anthracycline-induced death Blood, March 1, 2008; 111(5): 2866 - 2877. [Abstract] [Full Text] [PDF]

				L. Zhang, L. Gao, Y. Li, G. Lin, Y. Shao, K. Ji, H. Yu, J. Hu, D. V. Kalvakolanu, D. J. Kopecko, et al. Effects of Plasmid-Based Stat3-Specific Short Hairpin RNA and GRIM-19 on PC-3M Tumor Cell Growth Clin. Cancer Res., January 15, 2008; 14(2): 559 - 568. [Abstract] [Full Text] [PDF]

				J. L. Barclay, S. T. Anderson, M. J. Waters, and J. D. Curlewis Characterization of the SOCS3 Promoter Response to Prostaglandin E2 in T47D Cells Mol. Endocrinol., October 1, 2007; 21(10): 2516 - 2528. [Abstract] [Full Text] [PDF]

				S. Fukuda, M. Abematsu, H. Mori, M. Yanagisawa, T. Kagawa, K. Nakashima, A. Yoshimura, and T. Taga Potentiation of Astrogliogenesis by STAT3-Mediated Activation of Bone Morphogenetic Protein-Smad Signaling in Neural Stem Cells Mol. Cell. Biol., July 1, 2007; 27(13): 4931 - 4937. [Abstract] [Full Text] [PDF]

				M. Wang, L. Zhang, X. Han, J. Yang, J. Qian, S. Hong, F. Samaniego, J. Romaguera, and Q. Yi Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways Blood, June 15, 2007; 109(12): 5455 - 5462. [Abstract] [Full Text] [PDF]

				W. Komyod, M. Bohm, D. Metze, P. C. Heinrich, and I. Behrmann Constitutive Suppressor of Cytokine Signaling 3 Expression Confers a Growth Advantage to a Human Melanoma Cell Line Mol. Cancer Res., March 1, 2007; 5(3): 271 - 281. [Abstract] [Full Text] [PDF]