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

J. Biol. Chem., Vol. 280, Issue 28, 26491-26498, July 15, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/28/26491    most recent M503638200v1 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 Su, D. Articles by Gladyshev, V. N. Search for Related Content PubMed PubMed Citation Articles by Su, D. Articles by Gladyshev, V. N. Social Bookmarking                      What's this?

Mammalian Selenoprotein Thioredoxin-glutathione Reductase

ROLES IN DISULFIDE BOND FORMATION AND SPERM MATURATION^*

Dan Su, Sergey V. Novoselov, Qi-An Sun¶, Mohamed E. Moustafa||, You Zhou**, Richard Oko, Dolph L. Hatfield||, and Vadim N. Gladyshev

From the Department of Biochemistry and ^**Center for Biotechnology, University of Nebraska, Lincoln, Nebraska 68588, ^||NCI, National Institutes of Health, Bethesda, Maryland 20892, and the Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada

Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction.

Received for publication, April 4, 2005 , and in revised form, May 6, 2005.

^* This work was supported by Grant GM065204 from the National Institutes of Health (to V. N. G.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

These authors contributed equally to this work.

^¶ Present address: Dept. of Medicine, Duke University Medical Center, Durham, NC 27710.

To whom correspondence should be addressed. Dept. of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664. Tel.: 402-472-4948; Fax: 402-472-7842; E-mail: vgladyshev1{at}unl.edu.

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

This article has been cited by other articles:

				P. Dammeyer, A. E. Damdimopoulos, T. Nordman, A. Jimenez, A. Miranda-Vizuete, and E. S. J. Arner Induction of Cell Membrane Protrusions by the N-terminal Glutaredoxin Domain of a Rare Splice Variant of Human Thioredoxin Reductase 1 J. Biol. Chem., February 1, 2008; 283(5): 2814 - 2821. [Abstract] [Full Text] [PDF]

				M. Aichler, H. Algul, D. Behne, G. Holzlwimmer, B. Michalke, L. Quintanilla-Martinez, J. Schmidt, R. M. Schmid, and M. Brielmeier Selenium status alters tumour differentiation but not incidence or latency of pancreatic adenocarcinomas in Ela-TGF-{alpha} p53+/ mice Carcinogenesis, September 1, 2007; 28(9): 2002 - 2007. [Abstract] [Full Text] [PDF]

				B. Moghadaszadeh and A. H. Beggs Selenoproteins and Their Impact on Human Health Through Diverse Physiological Pathways. Physiology, October 1, 2006; 21(5): 307 - 315. [Abstract] [Full Text] [PDF]

				A. A. Turanov, D. Su, and V. N. Gladyshev Characterization of Alternative Cytosolic Forms and Cellular Targets of Mouse Mitochondrial Thioredoxin Reductase J. Biol. Chem., August 11, 2006; 281(32): 22953 - 22963. [Abstract] [Full Text] [PDF]

				B. Halliwell Reactive Species and Antioxidants. Redox Biology Is a Fundamental Theme of Aerobic Life Plant Physiology, June 1, 2006; 141(2): 312 - 322. [Full Text] [PDF]

				A. D. Ferguson, V. M. Labunskyy, D. E. Fomenko, D. Arac, Y. Chelliah, C. A. Amezcua, J. Rizo, V. N. Gladyshev, and J. Deisenhofer NMR Structures of the Selenoproteins Sep15 and SelM Reveal Redox Activity of a New Thioredoxin-like Family J. Biol. Chem., February 10, 2006; 281(6): 3536 - 3543. [Abstract] [Full Text] [PDF]

				J. Kohrle, F. Jakob, B. Contempre, and J. E. Dumont Selenium, the Thyroid, and the Endocrine System Endocr. Rev., December 1, 2005; 26(7): 944 - 984. [Abstract] [Full Text] [PDF]

				M. Maiorino, A. Roveri, L. Benazzi, V. Bosello, P. Mauri, S. Toppo, S. C. E. Tosatto, and F. Ursini Functional Interaction of Phospholipid Hydroperoxide Glutathione Peroxidase with Sperm Mitochondrion-associated Cysteine-rich Protein Discloses the Adjacent Cysteine Motif as a New Substrate of the Selenoperoxidase J. Biol. Chem., November 18, 2005; 280(46): 38395 - 38402. [Abstract] [Full Text] [PDF]