This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leo, C. P. Articles by Hsueh, A. J. W. Search for Related Content PubMed PubMed Citation Articles by Leo, C. P. Articles by Hsueh, A. J. W. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide OMIM Protein UniGene Substance via MeSH

DEFT, a Novel Death Effector Domain-Containing Molecule Predominantly Expressed in Testicular Germ Cells¹

Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, California 94305-5317

Address all correspondence and requests for reprints to: Aaron J. W. Hsueh, Department of Gynecology and Obstetrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305-5317. E-mail: aaron.hsueh{at}forsythe.stanford.edu

Apoptosis is a physiological process by which multicellular organisms eliminate unwanted cells. Death factors such as Fas ligand induce apoptosis by triggering a series of intracellular protein-protein interactions mediated by defined motifs found in the signaling molecules. One of these motifs is the death effector domain (DED), a stretch of about 80 amino acids that is shared by adaptors, regulators, and executors of the death factor pathway. We have identified the human and rat complementary DNAs encoding a novel protein termed DEFT (Death EFfector domain-containing Testicular molecule). The N-terminus of DEFT shows a high degree of homology to the DEDs found in FADD (an adaptor molecule) as well as procaspase-8/FLICE and procaspase-10/Mch4 (executors of the death program). Northern blot hybridization experiments have shown that the DEFT messenger RNA (mRNA) is expressed in a variety of human and rat tissues, with particularly abundant expression in the testis. In situ hybridization analysis further indicated the expression of DEFT mRNA in meiotic male germ cells. In a model of germ cell apoptosis induction, an increase in testis DEFT mRNA was found in immature rats after 2 days of treatment with a GnRH antagonist. Unlike FADD and procaspase-8/FLICE, overexpression of DEFT did not induce apoptosis in Chinese hamster ovary cells. Although cotransfection studies indicated that DEFT is incapable of modulating apoptosis effected by FADD and procaspase-8/FLICE, interactions between DEFT and uncharacterized DED-containing molecules in the testis remain to be studied in the future. In conclusion, we have identified a novel DED-containing protein with high expression in testis germ cells. This protein may be important in the regulation of death factor-induced apoptosis in the testis and other tissues.

This article has been cited by other articles:

				W. Roth, F. Stenner-Liewen, K. Pawlowski, A. Godzik, and J. C. Reed Identification and Characterization of DEDD2, a Death Effector Domain-containing Protein J. Biol. Chem., February 22, 2002; 277(9): 7501 - 7508. [Abstract] [Full Text] [PDF]

				J. C. Reed Mechanisms of Apoptosis Am. J. Pathol., November 1, 2000; 157(5): 1415 - 1430. [Abstract] [Full Text] [PDF]

				S. Y. Hsu and A. J. W. Hsueh Discovering New Hormones, Receptors, and Signaling Mediators in the Genomic Era Mol. Endocrinol., May 1, 2000; 14(5): 594 - 604. [Full Text]

				S. Y. Hsu and A. J. W. Hsueh Tissue-Specific Bcl-2 Protein Partners in Apoptosis: An Ovarian Paradigm Physiol Rev, April 1, 2000; 80(2): 593 - 614. [Abstract] [Full Text] [PDF]