Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Siah Ubiquitin Ligases Modulate Nodal Signaling during Zebrafish Embryonic Development

  • Kang, Nami (Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Won, Minho (Program in Genomics of Differentiation, Eunice Kennedy Shiver National Institute of Child Health and Human Development, National Institutes of Health) ;
  • Rhee, Myungchull (Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Ro, Hyunju (Department of Biological Sciences, College of Bioscience and Biotechnology, Chungnam National University)
  • Received : 2014.02.18
  • Accepted : 2014.03.31
  • Published : 2014.05.31
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Abstract

Siah acts as an E3 ubiquitin ligase that binds proteins destined for degradation. Extensive homology between siah and Drosophila Siah homologue (sina) suggests their important physiological roles during embryonic development. However, detailed functional studies of Siah in vertebrate development have not been carried out. Here we report that Siah2 specifically augments nodal related gene expression in marginal blastomeres at late blastula through early gastrula stages of zebrafish embryos. Siah2 dependent Nodal signaling augmentation is confirmed by cell-based reporter gene assays using 293T cells and 3TP-luciferase reporter plasmid. We also established a molecular hierarchy of Siah as a upstream regulator of FoxH1/Fast1 transcriptional factor in Nodal signaling. Elevated expression of nodal related genes by overexpression of Siah2 was enough to override the inhibitory effects of atv and lft2 on the Nodal signaling. In particular, E3 ubiquitin ligase activity of Siah2 is critical to limit the duration and/or magnitude of Nodal signaling. Additionally, since the embryos injected with Siah morpholinos mimicked the atv overexpression phenotype at least in part, our data support a model in which Siah is involved in mesendoderm patterning via modulating Nodal signaling.

Keywords

References

  1. Anuppalle, M., Maddirevula, S., Huh, T.R., and Rhee, M. (2013). Ubiquitin proteasome system networks in the neurological disorder. Anim. Cells Syst. 17, 383-387. https://doi.org/10.1080/19768354.2013.855256
  2. Attisano, L., Silvestri, C., Izzi, L., and Labbe, E. (2001). The transcriptional role of Smads and FAST (FoxH1) in TGF-$\beta$ and activin signalling. Mol. Cell. Endocrinol. 180, 3-11. https://doi.org/10.1016/S0303-7207(01)00524-X
  3. Bisgrove, B.W., Essner, J.J., and Yost, H.J. (1999). Regulation of midline development by antagonism of lefty and nodal signaling. Development 236, 3253-3262.
  4. Carthew, R.W., and Rubin, G.M. (1990). seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eye. Cell 63, 561-577. https://doi.org/10.1016/0092-8674(90)90452-K
  5. Chen, X., Weisberg, E., Fridmacher, V., Watanabe, M., Naco, G., and Whitman, M. (1997). Smad4 and FAST-1 in the assembly of activin-responsive factor. 389, 85-89. https://doi.org/10.1038/38008
  6. Erter, C.E., Solnica-Krezel, L., and Wright, C.V. (1998). Zebrafish nodal-related 2 encodes an early mesendodermal inducer signaling from the extraembryonic yolk syncytial layer. Dev. Biol. 204, 361-372. https://doi.org/10.1006/dbio.1998.9097
  7. Erter, C.E., Wilm, T.P., Basler, N., Wright, C.V., and Solnica-Krezel, L. (2001). Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo. Development 128, 3571-3583.
  8. Feldman, B., Gates, M.A., Egan, E.S., Dougan, S.T., Rennebeck, G., Sirotkin, H.I., Schier, A.F., and Talbot, W.S. (1998). Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395, 181-185. https://doi.org/10.1038/26013
  9. Frew, I.J., Hammond, V.E., Dickins, R.A., Quinn, J.M., Walkley, C.R., Sims, N.A., Schnall, R., Della, N.G., Holloway, A.J., Digby, M.R., et al. (2003). Generation and analysis of Siah2 mutant mice. Mol. Cell. Biol. 23, 9150-9161. https://doi.org/10.1128/MCB.23.24.9150-9161.2003
  10. Gore, A.V., Maegawa, A., Cheong, A., Gilligan, P.C., Weinberg, E.S., and Sampath, K. (2005). The zebrafish dorsal axis is apparent at the four-cell stage. Nature 438, 1030-1035. https://doi.org/10.1038/nature04184
  11. Gritsman, K., Zhang, J., Cheng, S., Heckscher, E., Talbot, W.S., and Schier, A.F. (1999). The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 97, 121-132. https://doi.org/10.1016/S0092-8674(00)80720-5
  12. House, CM., Frew, I.J., Huang, H.L., Wiche, G., Traficante, N., Nice, E., Catimel, B., and Bowtell, D.D. (2003). A binding motif for Siah ubiquitin ligase. Proc. Natl. Acad. Sci. USA 100, 3101-3106. https://doi.org/10.1073/pnas.0534783100
  13. House, C.M., Moller, A., and Bowtell, D.L. (2009). Siah protein: novel drug targets in the ras and hypoxia pathways. Cancer Res. 69, 8835-8838. https://doi.org/10.1158/0008-5472.CAN-09-1676
  14. Houston, D.W., and Wylie, C. (2005). Maternal Xenopus Zic2 negatively regulates Nodal-related gene expression during anteroposterior patterning. Development 132, 4845-4855. https://doi.org/10.1242/dev.02066
  15. Hu, G., Chung, Y.L., Glover, T., Valentine, V., Look, A.T., and Fearon, E.R. (1997). Characterization of human homologs of the Drosophila seven in absentia (sina) gene. Genomics 46, 103-111. https://doi.org/10.1006/geno.1997.4997
  16. Huelsken, J., and Birchmeier, W. (2001). New aspects of Wnt signaling pathways in higher vertebrates. Curr. Opin. Genet. Dev. 11, 547-553. https://doi.org/10.1016/S0959-437X(00)00231-8
  17. Iratni, R., Yan, Y.T., Chen, C., Ding, J., Zhang, Y., Price, S.M., Reinberg, D., and Shen, M.M. (2002). Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298, 1996-1999. https://doi.org/10.1126/science.1073405
  18. Johnsen, S.A., Subramaniam, M., Monroe, D.G., Janknecht, R., and Spelsberg, T.C. (2002). Modulation of transforming growth factor (TGF-$\beta$)/Smad transcriptional responses through targeted degradation of TGF-$\beta$-inducible early gene-1 by human seven in absentia homologue. J. Biol. Chem. 277, 30754-30759. https://doi.org/10.1074/jbc.M204812200
  19. Juuti-Uusitalo, K.M., Kaukinen, K., Maki, M., Tuimala, J., and Kainulainen, H. (2006). Gene expression in TGFbeta-induced epithelial cell differentiation in a three-dimensional intestinal epithelial cell differentiation model. BMC Genomics 7, 279. https://doi.org/10.1186/1471-2164-7-279
  20. Langdon, Y.G., and Mullins, M.C. (2011). Maternal and zygotic control of zebrafish dorsoventral axial patterning. Annu. Rev. Genet. 45, 357-377. https://doi.org/10.1146/annurev-genet-110410-132517
  21. Li, S., Li, Y., Carthew, R.W., and Lai, Z.C. (1997). Photoreceptor cell differentiation requires regulated proteolysis of the transcriptional repressor tramtrack. Cell 90, 469-478. https://doi.org/10.1016/S0092-8674(00)80507-3
  22. Liao, Y., Zhang, M., and Lonnerdal, B. (2012). Growth factor TGF-$\beta$ induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop. Genes Nutr. 8, 69-78.
  23. Liu, J., Stevens, J., Rote, C.A., Yost, H.J., Hu, Y., Neufeld, K.L., White, R.L., and Matsunami, N. (2001). Siah-1 mediates a novel $\beta$-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol. Cell 7, 927-936. https://doi.org/10.1016/S1097-2765(01)00241-6
  24. Lu, F.I., Thisse, C., and Thisse, B. (2011). Identification and mechanism of regulation of the zebrafish dorsal determinant. Proc. Natl. Acad. Sci. USA 108, 15876-15880. https://doi.org/10.1073/pnas.1106801108
  25. Matsuzawa, S., and Reed, J.C. (2001). Siah-1, SIP, and Ebi collaborate in a novel pathway for b-catenin degradation linked to p53 responses. Mol. Cell 7, 915-926. https://doi.org/10.1016/S1097-2765(01)00242-8
  26. Matsuzawa, S., Takayama, S., Froesch, B.A., Zapata, J.M., and Reed, J.C. (1998). p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1. EMBO J. 17, 2736-2747. https://doi.org/10.1093/emboj/17.10.2736
  27. Medhioub, M., Vaury, C., Hamelin, R., and Thomas, G. (2000). Lack of somatic mutation in the coding sequence of SIAH1 in tumors hemizygous for this candidate tumor suppressor gene. Int. J. Cancer 87, 794-797. https://doi.org/10.1002/1097-0215(20000915)87:6<794::AID-IJC5>3.0.CO;2-B
  28. Moller, A., House, C.M., Wong, C.S., Scanlon, D.B., Liu, M.C., Ronai, Z., and Bowtell, D.D. (2009). Inhibition of Siah ubiquitin ligase function. Oncogene 28, 289-296. https://doi.org/10.1038/onc.2008.382
  29. Nadeau, R.J., Toher, J.L., Yang, X., Kovalenko, D., and Friesel, R. (2006). Regulation of Sprouty2 stability by mammalian Sevenin-Absentia homolog 2. J. Cell Biochem. 100, 151-160.
  30. Pogoda, H.M., and Meyer, D. (2002). Zebrafish Smad7 is regulated by Smad3 and BMP signals. Dev. Dyn. 224, 334-349. https://doi.org/10.1002/dvdy.10113
  31. Pogoda, H.M., Solnica-Krezel, L., Driever, W., and Meyer, D. (2000). The zebrafish forkhead transcription factor FoxH1/Fast1 is a modulator of nodal signaling required for organizer formation. Curr. Biol. 10, 1041-1049. https://doi.org/10.1016/S0960-9822(00)00669-2
  32. Qi, J., Nakayama, K., Gaitonde, S., Goydos, J.S., Krajewski, S., Eroshkin, A., Bar-Sagi, D., Bowtell, D., and Ronai, Z. (2008). The ubiquitin ligase Siah2 regulates tumorigenesis and metastasis by HIF-dependent and -independent pathways. Proc. Natl. Acad. Sci. USA 105, 16713-16718. https://doi.org/10.1073/pnas.0804063105
  33. Qi, J., Kim, H., Scortegagna, M., and Ronai, Z.A. (2013). Regulators and effectors of Siah ubiquitin ligases. Cell Biochem. Biophys. 67, 15-24. https://doi.org/10.1007/s12013-013-9636-2
  34. Rebagliati, M.R., Toyama, R., Haffter, P., and Dawid, I.B. (1998). cyclops encodes a nodal-related factor involved in midline signaling. Proc. Natl. Acad. Sci. USA 95, 9932-9937. https://doi.org/10.1073/pnas.95.17.9932
  35. Ro, H., Kim, K.E., Huh, T.L., Lee, S.-K., and Rhee, M. (2003). Expression pattern of Siaz gene during the zebrafish embryonic development. Gene Exp. Patterns 3, 483-488. https://doi.org/10.1016/S1567-133X(03)00061-9
  36. Ro, H., Jang, Y., and Rhee, M. (2004a). The ring domain of Siaz, the zebrafish homologue of Drosophila seven in absentia, is essential for cellular growth arrest. Mol. Cells 17, 160-165.
  37. Ro, H., Soun, K., Kim, E-J., and Rhee, M. (2004b). Novel vector systems optimized for injecting in vitro-synthesized mRNA into zebrafish embryos. Mol. Cells 17, 373-376.
  38. Ro, H., Won, M., Lee, S.U., Kim, K.E., Huh, H.L., Kim, C.H., and Rhee, M. (2005). Sinup, a novel Siaz-interacting nuclear protein, modulates neural plate formation in the zebrafish embryos. Biochem. Biophys. Res. Commun. 332, 993-1003. https://doi.org/10.1016/j.bbrc.2005.05.053
  39. Robu, M.E., Larson, J.D., Nasevicius, A., Beiraghi, S., Brenner, C., Farber, S.A., and Ekker, S.C. (2007). p53 activation by knockdown technologies. PLoS Genet. 3, e78. https://doi.org/10.1371/journal.pgen.0030078
  40. Schier, A.F., and Talbot, W.S. (2001). Nodal signaling and the zebrafish organizer. Int. J. Dev. Biol. 45, 289-297.
  41. Schier, A.F., and Talbot, W.S. (2005). Molecular genetics of axis formation in zebrafish. Annu. Rev. Genet. 39, 561-613. https://doi.org/10.1146/annurev.genet.37.110801.143752
  42. Sirotkin, H.I., Gates, M.A., Kelly, P.D., Schier, A.F., and Talbot, W.S. (2000). Fast1 is required for the development of dorsal axial structures in zebrafish. Curr. Biol. 10, 1051-1054. https://doi.org/10.1016/S0960-9822(00)00679-5
  43. Tang, A.H., Neufeld, T.P., Kwan, E., and Rubin, G.M. (1997). PHYL acts to down-regulate TTK88, a transcriptional repressor of neuronal cell fates, by a SINA-dependent mechanism. Cell 90, 459-467. https://doi.org/10.1016/S0092-8674(00)80506-1
  44. Thisse, C., and Thisse, B. (1999). Antivin, a novel and divergent member of the TGF-$\beta$ superfamily, negatively regulates mesoderm induction. Development 126, 229-240.
  45. Thisse, B., Wright, C.V., and Thisse, C. (2000). Activin- and Nodalrelated factors control antero-posterior patterning of the zebrafish embryo. Nature 403, 425-428. https://doi.org/10.1038/35000200
  46. Westerfield, M. (1995). The Zebrafish book: a guide for the laboratory use of zebrafish (Danio rerio) (University of Oregon Press).
  47. Whitman, M. (2001). Nodal signaling in early vertebrate embryos: themes and variations. Dev. Cell 1, 605-617. https://doi.org/10.1016/S1534-5807(01)00076-4
  48. Wong, C.S., and Moler, A. (2013). Siah: a promising anticancer target. Cancer Res. 73, 2400-2406. https://doi.org/10.1158/0008-5472.CAN-12-4348

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