Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin II AT2 receptor-interacting proteins, ATIP M. Di Benedetto a,b,c,d,1 , I. Bièche e , F. Deshayes a,b,c,d,2 , S. Vacher e , S. Nouet a,b,c,d , V. Collura f , I. Seitz a,b,c,d,3 , S. Louis a,b,c,d,4 , P. Pineau g , D. Amsellem-Ouazana e,h , P.O. Couraud a,b,c,d , A.D. Strosberg a,b,c,d,f,5 , D. Stoppa-Lyonnet i , R. Lidereau e , C. Nahmias a,b,c,d, ⁎ a Institut Cochin, Département de Biologie Cellulaire, Paris, F-75014, France b Inserm, U567, Paris, F-75014, France c CNRS, UMR 8104, Paris, F-75014, France d Université Paris 5, Faculté de Médecine René Descartes, UM 3, Paris, F-75014, France e Inserm, U735, Centre René Huguenin, 92211 St Cloud, France f Hybrigenics SA, 3 impasse Reille, Paris, F-75014, France g Inserm U579, Unité d'Organisation Nucléaire et Oncogénèse, Institut Pasteur, Paris, France h Hopital Cochin, Université Paris 5, Department of Urology, Paris, F-75014, France i Laboratoire de Génétique Oncologique, Institut Curie, Paris, F-75005, France Received 27 February 2006; received in revised form 5 May 2006; accepted 18 May 2006 Available online 1 August 2006 Received by A. Bernardi Abstract The Mitochondrial Tumor suppressor 1 (MTUS1) gene is a newly identified candidate tumor suppressor gene at chromosomal position 8p22. We report here that MTUS1 encodes a family of proteins whose leader member (ATIP1) was previously isolated in our laboratory as a novel interacting partner of the angiotensin II AT2 receptor involved in growth inhibition (Nouet, JBC 279: 28989–97, 2004). The MTUS1 gene contains 17 coding exons distributed over 112 kb of genomic DNA. Alternative exon usage generates three major transcripts (ATIP1, ATIP3 and ATIP4), each showing different tissue distribution. ATIP polypeptides are identical in their carboxy-terminal region carrying four coiled-coil domains. In their amino-terminal portion, ATIP polypeptides exhibit distinct motifs for localisation in the cytosol, nucleus or cell membrane, suggesting that MTUS1 gene products may be involved in a variety of intracellular functions in an AT2-dependent and independent manner. ATIP1 is ubiquitous and highly expressed in the brain. ATIP3 is the major transcript in tissues (prostate, bladder, breast, ovary, colon) corresponding to cancer types with frequent loss of heterozygosity at 8p22. Interestingly, ATIP4 is a brain-specific transcript highly abundant in the cerebellum and fetal brain. High evolutionary conservation of ATIP amino-acid sequences suggests important biological roles for this new family of proteins in tumor suppression and/or brain function. © 2006 Elsevier B.V. All rights reserved. Keywords: ATIP; Brain; Cancer; Cerebellum; Human tissues; Real-time RT-PCR Gene 380 (2006) 127 – 136 www.elsevier.com/locate/gene Abbreviations: ATIP, AT2 receptor-interacting protein; ERK, extracellular-regulated kinase; MTUS1, mitochondrial tumor suppressor 1; TSG, tumor suppressor gene. ⁎ Corresponding author. Institut Cochin, Department of Cell Biology, 22 rue Mechain, 75014 Paris, France.Tel.: +33 1 40 51 64 10; fax: +33 1 40 51 64 30. E-mail address: nahmias@cochin.inserm.fr (C. Nahmias). 1 Present address: CNRS UMR7033, Equipe de Pharmacologie, Université Paris 13, 74 rue Marcel Cachin, 93017 Bobigny, France. 2 Present address: CNRS UMR7592, Institut Jacques Monod, Université Paris VI et Paris VII, Paris, France. 3 Present address: Deutsches Herzzentrum Muenchen, Germany. 4 Present address: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, 3084, Australia. 5 Present address: Department of Infectology, The Scripps Research Institute—Florida, USA. 0378-1119/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.gene.2006.05.021