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Genomic organization and expression profile of the human and mouse WAVE gene family

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Abstract

The WAVE gene family, which contains three members, has been shown to play a major role in the actin polymerization and cytoskeleton organization processes. We have identified the WAVE3 gene from Chromosome (Chr) 13q12, as being involved in one of the breakpoints of a t(1:13)(q21:q12) reciprocal translocation, in a patient with ganglioneuroblastoma (Sossey-Alaoui et al. 2002; Oncogene 21: 5967–5974). We have also reported the cloning of the mouse Wave3. During our analysis of the human gene map, we also noted that WAVE2 maps to Chr region lp35-36, which frequently undergoes loss of heterozygosity and deletion in advanced stage neuroblastoma. These data clearly indicate a possible involvement of the WAVE genes in the pathogenesis of neuroblastoma. In this study, we report the complete genomic organization and expression profile of the three human WAVE genes and their mouse orthologs. We show that the WAVE genes have distinctive expression patterns in both adult and fetal human and mouse tissues. We also show a high level of conservation between these genes, in both the nucleotide and protein sequences. We finally show that the genomic structure is highly conserved among these genes and that the mouse Wave genes map to chromosome regions that have synteny in the human genome. The gene content in these syntenic regions is also conserved, suggesting that the WAVE genes are derived from a common ancient ancestor by genome duplication. The genomic characterization and expression analysis of the WAVE genes provide the basis towards understanding the function of these genes. It also provides the first steps towards the development of mouse models for the role of the WAVE genes in actin and cytoskeleton organization in general, and in the development of neuroblastoma in particular.

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References

  1. A Bauer L Savelyeva A Claas C Praml F Berthold et al. (2001) ArticleTitleSmallest region of overlapping deletion in 1p36 in human neuroblastoma: a 1 Mbp cosmid and PAC contig. Genes Chromosomes Cancer 31 228–239 Occurrence Handle10.1002/gcc.1139 Occurrence Handle1:CAS:528:DC%2BD3MXkslClsLk%3D Occurrence Handle11391793

    Article  CAS  PubMed  Google Scholar 

  2. N Benachenhou I Massy J Vacher (2002) ArticleTitleCharacterization and expression analyses of the mouse Wiskott-Aldrich syndrome protein (WASP) family member Wave1/Scar. Genes 290 131–140 Occurrence Handle10.1016/S0378-1119(02)00560-7 Occurrence Handle1:CAS:528:DC%2BD38XktlartLc%3D

    Article  CAS  Google Scholar 

  3. Z Biesova C Piccoli WT Wong (1997) ArticleTitleIsolation and characterization of e3B1, an eps8 binding protein that regulates cell growth. Oncogene 14 233–241 Occurrence Handle10.1038/sj.onc.1200822 Occurrence Handle1:CAS:528:DyaK2sXnsFChsg%3D%3D Occurrence Handle9010225

    Article  CAS  PubMed  Google Scholar 

  4. MF Carlier P Nioche I Broutin-L'Hermite R Boujemaa C Le Clainche et al. (2000) ArticleTitleGRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex. J Biol Chem 275 21946–21952 Occurrence Handle10.1074/jbc.M000687200 Occurrence Handle1:CAS:528:DC%2BD3cXltFGjtb4%3D Occurrence Handle10781580

    Article  CAS  PubMed  Google Scholar 

  5. MD Cooper HP Chae JT Lowman W Krivit RA Good (1968) ArticleTitleWiskott-Aldrich syndrome: an immunologic deficiency disease involving the afferent limb of immunity. Am J Med 44 499–513 Occurrence Handle1:STN:280:CCeC28rmtVE%3D Occurrence Handle4171085

    CAS  PubMed  Google Scholar 

  6. RW DeBry MF Seldin (1996) ArticleTitleHuman/mouse homology relationships. Genomics 33 337–351 Occurrence Handle10.1006/geno.1996.0209 Occurrence Handle1:CAS:528:DyaK28XjtVWjsLg%3D Occurrence Handle8660993

    Article  CAS  PubMed  Google Scholar 

  7. JMJ Derry HD Ochs U Francke (1994) ArticleTitleIsolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell 78 635–644 Occurrence Handle1:CAS:528:DyaK2cXmt1ymtr0%3D Occurrence Handle8069912

    CAS  PubMed  Google Scholar 

  8. M Fukuoka S Suetsugu H Miki K Fukami T Endo et al. (2001) ArticleTitleA novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42. J Cell Biol 152 471–482 Occurrence Handle10.1083/jcb.152.3.471 Occurrence Handle1:CAS:528:DC%2BD3MXhtVGqtLs%3D Occurrence Handle11157975

    Article  CAS  PubMed  Google Scholar 

  9. S Krugmann I Jordens K Gevaert M Driessens J Van-dekerckhove et al. (2001) ArticleTitleCdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr Biol 11 1645–1655 Occurrence Handle10.1016/S0960-9822(01)00506-1 Occurrence Handle1:CAS:528:DC%2BD3MXot1Oktrg%3D Occurrence Handle11696321

    Article  CAS  PubMed  Google Scholar 

  10. L MacCarthy-Morrogh HB Gaspar YC Wang F Katz L Thompson et al. (1998) ArticleTitleAbsence of expression of the Wiskott-Aldrich syndrome protein in peripheral blood cells of Wiskott-Aldrich syndrome patients. Clin Immunol Immunopathol 88 22–27 Occurrence Handle1:CAS:528:DyaK1cXlsVCgsrw%3D Occurrence Handle9683546

    CAS  PubMed  Google Scholar 

  11. JM Maris C Guo D Blake PS White MB Hogarty et al. (2001) ArticleTitleComprehensive analysis of chromosome 1p deletions in neuroblastoma. Med Pediatr Oncol 36 32–36 Occurrence Handle10.1002/1096-911X(20010101)36:1<32::AID-MPO1009>3.0.CO;2-0 Occurrence Handle1:STN:280:DC%2BD3MvhsV2hsA%3D%3D Occurrence Handle11464900

    Article  CAS  PubMed  Google Scholar 

  12. GE Meyer E Shelden B Kim EL Feldman (2001) ArticleTitleInsulin-like growth factor I stimulates motility in human neuroblastoma cells. Oncogene 20 7542–7550 Occurrence Handle10.1038/sj.onc.1204927 Occurrence Handle1:CAS:528:DC%2BD3MXovVyrt7c%3D Occurrence Handle11709726

    Article  CAS  PubMed  Google Scholar 

  13. AJ Michalski FE Cotter JK Cowell (1992) ArticleTitleIsolation of chromosome-specific DNA sequences from an Alu polymerase chain reaction library to define the breakpoint in a patient with a constitutional translocation t(1;13) (q22;q12) and ganglioneuroblastoma. Oncogene 7 1595–1602 Occurrence Handle1:CAS:528:DyaK2cXisVGktw%3D%3D Occurrence Handle1630820

    CAS  PubMed  Google Scholar 

  14. H Miki S Suetsugu T Takenawa (1998) ArticleTitleWAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J 17 6932–6941 Occurrence Handle1:CAS:528:DyaK1MXivFaqtQ%3D%3D Occurrence Handle9843499

    CAS  PubMed  Google Scholar 

  15. H Miki T Takenawa (2002) ArticleTitleWAVE2 serves a functional partner of IRSp53 by regulating its interaction with Rac. Biochem Biophys Res Commun 293 93–99 Occurrence Handle10.1016/S0006-291X(02)00218-8 Occurrence Handle1:CAS:528:DC%2BD38XksVGitrg%3D Occurrence Handle12054568

    Article  CAS  PubMed  Google Scholar 

  16. H Miki H Yamaguchi S Suetsugu T Takenawa (2000) ArticleTitleIRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 408 732–735 Occurrence Handle10.1038/35047107 Occurrence Handle1:CAS:528:DC%2BD3cXptVCqs74%3D Occurrence Handle11130076

    Article  CAS  PubMed  Google Scholar 

  17. TJ Mitchison LP Cramer (1996) ArticleTitleActin-based cell motility and cell locomotion. Cell 84 371–379 Occurrence Handle1:CAS:528:DyaK28XhtFWqtrw%3D Occurrence Handle8608590

    CAS  PubMed  Google Scholar 

  18. T Nagase N Seki K Ishikawa M Orira Y Kawarabayasi et al. (1996) ArticleTitlePrediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201–KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res 3 321–329 Occurrence Handle1:CAS:528:DyaK28Xntlyrs74%3D Occurrence Handle9039502

    CAS  PubMed  Google Scholar 

  19. K Oda T Shiratsuchi H Nishimori J Inazawa H Yoshikawa et al. (1999) ArticleTitleIdentification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1. Cytogenet Cell Genet 84 75–82 Occurrence Handle10.1159/000015219 Occurrence Handle1:CAS:528:DyaK1MXjvFemtbw%3D Occurrence Handle10343108

    Article  CAS  PubMed  Google Scholar 

  20. Y Okamura-Oho T Miyashita K Ohmi M Yamada (1999) ArticleTitleDentatorubral-pallidoluysian atrophy protein interacts through a proline-rich region near polyglutamine with the SH3 domain of an insulin receptor tyrosine kinase substrate. Hum Mol Genet 8 947–957 Occurrence Handle10.1093/hmg/8.6.947 Occurrence Handle1:CAS:528:DyaK1MXjs1Wntr8%3D Occurrence Handle10332026

    Article  CAS  PubMed  Google Scholar 

  21. R Rohatgi P Nollau H Ho Hy MW Kirschner BJ Mayer (2001) ArticleTitleNck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway. J Biol Chem 276 26448–26452 Occurrence Handle10.1074/jbc.M103856200 Occurrence Handle1:CAS:528:DC%2BD3MXlsVKnt70%3D Occurrence Handle11340081

    Article  CAS  PubMed  Google Scholar 

  22. K Sossey-Alaoui G Su E Malaj B Roe JK Cowell (2002) ArticleTitleWAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with ganglioneuroblastoma. Oncogene 21 5967–5974 Occurrence Handle10.1038/sj.onc.1205734 Occurrence Handle1:CAS:528:DC%2BD38Xmt1Wntr8%3D Occurrence Handle12185600

    Article  CAS  PubMed  Google Scholar 

  23. R Spitz B Hero F Westermann K Ernestus M Schwab et al. (2002) ArticleTitleFluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations. Genes Chromosomes Cancer 34 299–305 Occurrence Handle10.1002/gcc.10070 Occurrence Handle1:CAS:528:DC%2BD38XltVSltbw%3D Occurrence Handle12007190

    Article  CAS  PubMed  Google Scholar 

  24. S Suetsugu H Miki T Takenawa (1999) ArticleTitle) Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex. Biochem Biophys Res Commun 260 296–302 Occurrence Handle10.1006/bbrc.1999.0894 Occurrence Handle1:CAS:528:DyaK1MXjvFWru7w%3D Occurrence Handle10381382

    Article  CAS  PubMed  Google Scholar 

  25. T Takenawa H Miki (2001) ArticleTitleWASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J Cell Sci 114 1801–1809 Occurrence Handle1:CAS:528:DC%2BD3MXktFWrtbs%3D Occurrence Handle11329366

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Tamara Ranalli, PhD, and Lisa Wylie for their technical assistance. This research was supported in part by a grant from the Association for Research on Children Cancer #62-3027-01 to K. Sossey-Alaoui, Institutional Research Grant #IRG02-197-01 from the American Cancer Society to K. Sossey-Alaoui, and by the RPCI's NCI-funded Cancer Center Support Grant, CA16056.

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Correspondence to Khalid Sossey-Alaoui.

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Sossey-Alaoui, K., Head, K., Nowak, N. et al. Genomic organization and expression profile of the human and mouse WAVE gene family . Mamm Genome 14, 314–322 (2003). https://doi.org/10.1007/s00335-002-2247-7

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  • DOI: https://doi.org/10.1007/s00335-002-2247-7

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