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This Article Full Text Full Text (PDF) All Versions of this Article: 71/6/1980    most recent biolreprod.104.032805v1 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 Modarressi, M. H. Articles by van der Hoorn, F. A. Search for Related Content PubMed PubMed Citation Articles by Modarressi, M. H. Articles by van der Hoorn, F. A. Agricola Articles by Modarressi, M. H. Articles by van der Hoorn, F. A.

A Novel Testicular RhoGAP-Domain Protein Induces Apoptosis¹

Department of Biochemistry and Molecular Biology,⁴ University of Calgary, Calgary, Alberta, Canada T2N 4N1 Department of Anatomy and Cell Biology,⁵ McGill University, Montreal, Quebec, Canada H3A 2T5 Departments Endocrinology, Faculty of Biology and of Cell Biology,⁶ UMCU, Utrecht University, Utrecht, The Netherlands

The GTPase-activating proteins (GAPs) accelerate the hydrolysis of GTP to GDP by small GTPases. The GTPases play diverse roles in many cellular processes, including proliferation, cell motility, endocytosis, nuclear import/export, and nuclear membrane formation. Little is known about GAP-domain proteins in spermatogenesis. We isolated a novel RhoGAP domain-containing tGAP1 protein from male germ cells that exhibits unusual properties. The tGAP1 is expressed at low levels in early spermatogonia. Robust transcription initiates in midpachytene spermatocytes and continues after meiosis. The 175-kDa tGAP1 protein localizes to the cytoplasm of spermatocytes and to the cytoplasm and nucleus in spermatids. The protein contains four GAP domain-related sequences, in contrast to all other GAP proteins that harbor one such domain. No activity toward RhoA, Rac1, or Cdc42 could be detected. Results of transfection studies in various somatic cells indicated that low-level tGAP1 expression significantly slows down the cell cycle. Expression of higher levels of tGAP1 by infection of somatic cells with recombinant adenoviruses demonstrated that tGAP1 efficiently induces apoptosis, which to our knowledge is the first such demonstration for a RhoGAP protein. Based on its subcellular location in spermatids and its activity, tGAP1 may play a role in nuclear import/export.

¹ Supported by grants from the Canadian Institutes of Health Research (CIHR) to F.A.v.d.H. and from the Canadian Cancer Society to N.L.-V., who is also a recipient of a CIHR new investigator award.

² Correspondence: Frans A. van der Hoorn, Department of Biochemistry & Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. FAX: 403 210 8109; fvdhoorn{at}ucalgary.ca

³ Current address: Department of Genetics, Tehran University of Medical Sciences, Tehran, Iran

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