JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M100380200 on April 30, 2001

J. Biol. Chem., Vol. 276, Issue 27, 24843-24854, July 6, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/27/24843    most recent
M100380200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ma, X.
Right arrow Articles by Kalvakolanu, D. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ma, X.
Right arrow Articles by Kalvakolanu, D. V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Regulation of Interferon and Retinoic Acid-induced Cell Death Activation through Thioredoxin Reductase*

Xinrong MaDagger , Sreenivasu KarraDagger , Wei GuoDagger , Daniel J. LindnerDagger §, Jiadi HuDagger , Jon E. AngellDagger , Edward R. HofmannDagger , Sekhar P. M. ReddyDagger ||, and Dhananjaya V. KalvakolanuDagger **

From the Dagger  Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, Maryland 21201 and || Department of Environmental Sciences, The Johns Hopkins University School of Public Health, Baltimore, Maryland

Interferons (IFNs) and retinoids are potent biological response modifiers. The IFN-beta and all-trans-retinoic acid combination, but not these single agents individually, induces death in several tumor cell lines. To elucidate the molecular basis for these actions, we have employed an antisense knockout approach to identify the gene products that mediate cell death and isolated several genes associated with retinoid-IFN-induced mortality (GRIMs). One of the GRIM cDNAs, GRIM-12, was identical to human thioredoxin reductase (TR). To define the functional relevance of TR to cell death and to define its mechanism of death-modulating functions, we generated mutants of TR and studied their influence on the IFN/RA-induced death regulatory functions of caspases. Wild-type TR activates cell death that was inhibited in the presence of caspase inhibitors or catalytically inactive caspases. A mutant TR, lacking the active site cysteines, inhibits the cell death induced by caspase 8. IFN/all-trans-retinoic acid-induced cytochrome c release from the mitochondrion was promoted in the presence of wild type and was inhibited in the presence of mutant TR. We find that TR modulates the activity of caspase 8 to promote death. This effect is in part caused by the stimulation of death receptor gene expression. These studies identify a new mechanism of cell death regulation by the IFN/all-trans-retinoic acid combination involving redox enzymes.

* This work was supported by National Cancer Institute Grants CA 78282 and CA 71401 (to D. V. K.). S. P. M. R. is supported by National Institutes of Health Grant HL-58122.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH 44195.

Present address: The Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.

** To whom correspondence should be addressed. Tel.: 410-328-1396; Fax: 410-328-1397; E-mail: dkalvako@umaryland.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. Kalakonda, S. C. Nallar, D. J. Lindner, J. Hu, S. P. Reddy, and D. V. Kalvakolanu
Tumor-Suppressive Activity of the Cell Death Activator GRIM-19 on a Constitutively Active Signal Transducer and Activator of Transcription 3
Cancer Res., July 1, 2007; 67(13): 6212 - 6220.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. E. Damdimopoulos, A. Miranda-Vizuete, E. Treuter, J.-A. Gustafsson, and G. Spyrou
An Alternative Splicing Variant of the Selenoprotein Thioredoxin Reductase Is a Modulator of Estrogen Signaling
J. Biol. Chem., September 10, 2004; 279(37): 38721 - 38729.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Ramos, A. N. Lane, D. Hollingworth, and T. W.-M. Fan
Secondary structure and stability of the selenocysteine insertion sequences (SECIS) for human thioredoxin reductase and glutathione peroxidase
Nucleic Acids Res., March 16, 2004; 32(5): 1746 - 1755.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Anestal and E. S. J. Arner
Rapid Induction of Cell Death by Selenium-compromised Thioredoxin Reductase 1 but Not by the Fully Active Enzyme Containing Selenocysteine
J. Biol. Chem., April 25, 2003; 278(18): 15966 - 15972.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. J. Lindner, X. Ma, J. Hu, S. Karra, and D. V. Kalvakolanu
Thioredoxin Reductase Plays a Critical Role in IFN Retinoid-mediated Tumor-Growth Control in Vivo
Clin. Cancer Res., October 1, 2002; 8(10): 3210 - 3218.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
T. Seo, D. Lee, Y. S. Shim, J. E. Angell, N. V. Chidambaram, D. V. Kalvakolanu, and J. Choe
Viral Interferon Regulatory Factor 1 of Kaposi's Sarcoma-Associated Herpesvirus Interacts with a Cell Death Regulator, GRIM19, and Inhibits Interferon/Retinoic Acid-Induced Cell Death
J. Virol., July 29, 2002; 76(17): 8797 - 8807.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Ma, J. Hu, D. J. Lindner, and D. V. Kalvakolanu
Mutational Analysis of Human Thioredoxin Reductase 1. EFFECTS ON p53-MEDIATED GENE EXPRESSION AND INTERFERON AND RETINOIC ACID-INDUCED CELL DEATH
J. Biol. Chem., June 14, 2002; 277(25): 22460 - 22468.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Hentze, I. Schmitz, M. Latta, A. Krueger, P. H. Krammer, and A. Wendel
Glutathione Dependence of Caspase-8 Activation at the Death-inducing Signaling Complex
J. Biol. Chem., February 8, 2002; 277(7): 5588 - 5595.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.