This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hu, G.
Right arrow Articles by Fearon, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hu, G.
Right arrow Articles by Fearon, E. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 1999, p. 724-732, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Siah-1 N-Terminal RING Domain Is Required for Proteolysis Function, and C-Terminal Sequences Regulate Oligomerization and Binding to Target Proteins

Gang Hu1 and Eric R. Fearon1,2,3,4,*

Division of Molecular Medicine and Genetics, Department of Internal Medicine,1 Department of Human Genetics,2 Department of Pathology,3 and The Cancer Center,4 University of Michigan Medical Center, Ann Arbor, Michigan

Received 26 June 1998/Accepted 1 October 1998

The Drosophila seven in absentia (sina) gene was initially discovered because its inactivation leads to R7 photoreceptor defects. Recent data indicate that Sina binds to the Sevenless pathway protein Phyllopod, and together they mediate degradation of Tramtrack, a transcriptional repressor of R7 cell fate. Independent studies have shown that Sina and its highly related mammalian homologues Siah-1 and Siah-2 bind to the DCC (deleted in colorectal cancer) protein and promote its proteolysis via the ubiquitin-proteasome pathway. To determine the roles of mammalian Siahs in proteolysis and their interactions with target proteins, we sought to define Siah-1 domains critical for regulation of DCC. Mutant Siah-1 proteins, harboring missense mutations in the carboxy (C)-terminal domain analogous to those present in Drosophila sina loss-of-function alleles, failed to promote DCC degradation. Point mutations and deletion of the amino (N)-terminal RING finger domain of Siah-1 abrogated its ability to promote DCC proteolysis. In the course of defining Siah-1 sequences required for DCC degradation, we found that Siah-1 is itself rapidly degraded via the proteasome pathway, and RING domain mutations stabilized the Siah-1 protein. Siah-1 was found to oligomerize with itself and other Sina and Siah proteins via C-terminal sequences. Finally, evidence that endogenous Siah-1 regulates DCC proteolysis in cells was obtained through studies of an apparent dominant negative mutant of Siah-1, as well as via an antisense approach. The data indicate that the Siah-1 N-terminal RING domain is required for its proteolysis function, while the C-terminal sequences regulate oligomerization and binding to target proteins, such as DCC.

* Corresponding author. Mailing address: Division of Molecular Medicine and Genetics, University of Michigan Medical Center, 4301 MSRB III, Box 0638, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0638. Phone: (734) 764-1549. Fax: (734) 647-7979. E-mail: efearon{at}mmg.im.med.umich.edu.

Molecular and Cellular Biology, January 1999, p. 724-732, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wong, W., Goehring, A. S., Kapiloff, M. S., Langeberg, L. K., Scott, J. D. (2008). mAKAP Compartmentalizes Oxygen-Dependent Control of HIF-1{alpha}. Sci Signal 1: ra18-ra18 [Abstract] [Full Text]  
  • Ahmed, A. U., Schmidt, R. L., Park, C. H., Reed, N. R., Hesse, S. E., Thomas, C. F., Molina, J. R., Deschamps, C., Yang, P., Aubry, M. C., Tang, A. H. (2008). Effect of Disrupting Seven-in-Absentia Homolog 2 Function on Lung Cancer Cell Growth. JNCI J Natl Cancer Inst 100: 1606-1629 [Abstract] [Full Text]  
  • Den Herder, G., De Keyser, A., De Rycke, R., Rombauts, S., Van de Velde, W., Clemente, M. R., Verplancke, C., Mergaert, P., Kondorosi, E., Holsters, M., Goormachtig, S. (2008). Seven in Absentia Proteins Affect Plant Growth and Nodulation in Medicago truncatula. Plant Physiol. 148: 369-382 [Abstract] [Full Text]  
  • Kramer, O. H., Muller, S., Buchwald, M., Reichardt, S., Heinzel, T. (2008). Mechanism for ubiquitylation of the leukemia fusion proteins AML1-ETO and PML-RAR{alpha}. FASEB J. 22: 1369-1379 [Abstract] [Full Text]  
  • Lee, J. T., Wheeler, T. C., Li, L., Chin, L.-S. (2008). Ubiquitination of {alpha}-synuclein by Siah-1 promotes {alpha}-synuclein aggregation and apoptotic cell death. Hum Mol Genet 17: 906-917 [Abstract] [Full Text]  
  • Abada, R., Dreyfuss-Grossman, T., Herman-Bachinsky, Y., Geva, H., Masa, S.-R., Sarid, R. (2008). SIAH-1 Interacts with the Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORF45 Protein and Promotes Its Ubiquitylation and Proteasomal Degradation. J. Virol. 82: 2230-2240 [Abstract] [Full Text]  
  • Capul, A. A., Perez, M., Burke, E., Kunz, S., Buchmeier, M. J., de la Torre, J. C. (2007). Arenavirus Z-Glycoprotein Association Requires Z Myristoylation but Not Functional RING or Late Domains. J. Virol. 81: 9451-9460 [Abstract] [Full Text]  
  • Jung, J. K., Kwun, H. J., Lee, J.-O., Arora, P., Jang, K. L. (2007). Hepatitis B virus X protein differentially affects the ubiquitin-mediated proteasomal degradation of beta-catenin depending on the status of cellular p53. J. Gen. Virol. 88: 2144-2154 [Abstract] [Full Text]  
  • Murcia-Flores, L., Lorca-Pascual, J. M., Garre, V., Torres-Martinez, S., Ruiz-Vazquez, R. M. (2007). Non-AUG Translation Initiation of a Fungal RING Finger Repressor Involved in Photocarotenogenesis. J. Biol. Chem. 282: 15394-15403 [Abstract] [Full Text]  
  • Park, S., Gwak, J., Cho, M., Song, T., Won, J., Kim, D.-E., Shin, J.-G., Oh, S. (2006). Hexachlorophene Inhibits Wnt/beta-Catenin Pathway by Promoting Siah-Mediated beta-Catenin Degradation. Mol. Pharmacol. 70: 960-966 [Abstract] [Full Text]  
  • Bae, B.-I., Hara, M. R., Cascio, M. B., Wellington, C. L., Hayden, M. R., Ross, C. A., Ha, H. C., Li, X.-J., Snyder, S. H., Sawa, A. (2006). Mutant Huntingtin: Nuclear translocation and cytotoxicity mediated by GAPDH. Proc. Natl. Acad. Sci. USA 103: 3405-3409 [Abstract] [Full Text]  
  • Xu, Z., Sproul, A., Wang, W., Kukekov, N., Greene, L. A. (2006). Siah1 Interacts with the Scaffold Protein POSH to Promote JNK Activation and Apoptosis. J. Biol. Chem. 281: 303-312 [Abstract] [Full Text]  
  • Jang, K. L., Shackelford, J., Seo, S. Y., Pagano, J. S. (2005). Up-regulation of {beta}-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells. Proc. Natl. Acad. Sci. USA 102: 18431-18436 [Abstract] [Full Text]  
  • Santelli, E., Leone, M., Li, C., Fukushima, T., Preece, N. E., Olson, A. J., Ely, K. R., Reed, J. C., Pellecchia, M., Liddington, R. C., Matsuzawa, S.-i. (2005). Structural Analysis of Siah1-Siah-interacting Protein Interactions and Insights into the Assembly of an E3 Ligase Multiprotein Complex. J. Biol. Chem. 280: 34278-34287 [Abstract] [Full Text]  
  • Oliver, P. L., Bitoun, E., Clark, J., Jones, E. L., Davies, K. E. (2004). Mediation of Af4 protein function in the cerebellum by Siah proteins. Proc. Natl. Acad. Sci. USA 101: 14901-14906 [Abstract] [Full Text]  
  • Kim, H., Jeong, W., Ahn, K., Ahn, C., Kang, S. (2004). Siah-1 Interacts with the Intracellular Region of Polycystin-1 and Affects Its Stability via the Ubiquitin-Proteasome Pathway. J. Am. Soc. Nephrol. 15: 2042-2049 [Abstract] [Full Text]  
  • Venables, J. P., Dalgliesh, C., Paronetto, M. P., Skitt, L., Thornton, J. K., Saunders, P. T., Sette, C., Jones, K. T., Elliott, D. J. (2004). SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome. Hum Mol Genet 13: 1525-1534 [Abstract] [Full Text]  
  • Moriyoshi, K., Iijima, K., Fujii, H., Ito, H., Cho, Y., Nakanishi, S. (2004). Seven in absentia homolog 1A mediates ubiquitination and degradation of group 1 metabotropic glutamate receptors. Proc. Natl. Acad. Sci. USA 101: 8614-8619 [Abstract] [Full Text]  
  • Liani, E., Eyal, A., Avraham, E., Shemer, R., Szargel, R., Berg, D., Bornemann, A., Riess, O., Ross, C. A., Rott, R., Engelender, S. (2004). Ubiquitylation of synphilin-1 and {alpha}-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease. Proc. Natl. Acad. Sci. USA 101: 5500-5505 [Abstract] [Full Text]  
  • Fanelli, M., Fantozzi, A., De Luca, P., Caprodossi, S., Matsuzawa, S.-i., Lazar, M. A., Pelicci, P. G., Minucci, S. (2004). The Coiled-coil Domain Is the Structural Determinant for Mammalian Homologues of Drosophila Sina-mediated Degradation of Promyelocytic Leukemia Protein and Other Tripartite Motif Proteins by the Proteasome. J. Biol. Chem. 279: 5374-5379 [Abstract] [Full Text]  
  • Nagano, Y., Yamashita, H., Takahashi, T., Kishida, S., Nakamura, T., Iseki, E., Hattori, N., Mizuno, Y., Kikuchi, A., Matsumoto, M. (2003). Siah-1 Facilitates Ubiquitination and Degradation of Synphilin-1. J. Biol. Chem. 278: 51504-51514 [Abstract] [Full Text]  
  • Frew, I. J., Hammond, V. E., Dickins, R. A., Quinn, J. M. W., Walkley, C. R., Sims, N. A., Schnall, R., Della, N. G., Holloway, A. J., Digby, M. R., Janes, P. W., Tarlinton, D. M., Purton, L. E., Gillespie, M. T., Bowtell, D. D. L. (2003). Generation and Analysis of Siah2 Mutant Mice. Mol. Cell. Biol. 23: 9150-9161 [Abstract] [Full Text]  
  • Topol, L., Jiang, X., Choi, H., Garrett-Beal, L., Carolan, P. J., Yang, Y. (2003). Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent {beta}-catenin degradation. JCB 162: 899-908 [Abstract] [Full Text]  
  • Okabe, H., Satoh, S., Furukawa, Y., Kato, T., Hasegawa, S., Nakajima, Y., Yamaoka, Y., Nakamura, Y. (2003). Involvement of PEG10 in Human Hepatocellular Carcinogenesis through Interaction with SIAH1. Cancer Res. 63: 3043-3048 [Abstract] [Full Text]  
  • House, C. M., Frew, I. J., Huang, H.-L., Wiche, G., Traficante, N., Nice, E., Catimel, B., Bowtell, D. D. L. (2003). A binding motif for Siah ubiquitin ligase. Proc. Natl. Acad. Sci. USA 100: 3101-3106 [Abstract] [Full Text]  
  • Kreft, S. G., Nassal, M. (2003). hRUL138, a novel human RNA-binding RING-H2 ubiquitin-protein ligase. J. Cell Sci. 116: 605-616 [Abstract] [Full Text]  
  • Frew, I. J., Dickins, R. A., Cuddihy, A. R., Del Rosario, M., Reinhard, C., O'Connell, M. J., Bowtell, D. D. L. (2002). Normal p53 Function in Primary Cells Deficient for Siah Genes. Mol. Cell. Biol. 22: 8155-8164 [Abstract] [Full Text]  
  • Li, S., Xu, C., Carthew, R. W. (2002). Phyllopod Acts as an Adaptor Protein To Link the Sina Ubiquitin Ligase to the Substrate Protein Tramtrack. Mol. Cell. Biol. 22: 6854-6865 [Abstract] [Full Text]  
  • Johnsen, S. A., Subramaniam, M., Monroe, D. G., Janknecht, R., Spelsberg, T. C. (2002). Modulation of Transforming Growth Factor beta (TGFbeta )/Smad Transcriptional Responses through Targeted Degradation of TGFbeta -inducible Early Gene-1 by Human Seven in Absentia Homologue. J. Biol. Chem. 277: 30754-30759 [Abstract] [Full Text]  
  • Hanai, J.-i., Gloy, J., Karumanchi, S. A., Kale, S., Tang, J., Hu, G., Chan, B., Ramchandran, R., Jha, V., Sukhatme, V. P., Sokol, S. (2002). Endostatin is a potential inhibitor of Wnt signaling. JCB 158: 529-539 [Abstract] [Full Text]  
  • Dickins, R. A., Frew, I. J., House, C. M., O'Bryan, M. K., Holloway, A. J., Haviv, I., Traficante, N., de Kretser, D. M., Bowtell, D. D. L. (2002). The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice. Mol. Cell. Biol. 22: 2294-2303 [Abstract] [Full Text]  
  • Wheeler, T. C., Chin, L.-S., Li, Y., Roudabush, F. L., Li, L. (2002). Regulation of Synaptophysin Degradation by Mammalian Homologues of Seven in Absentia. J. Biol. Chem. 277: 10273-10282 [Abstract] [Full Text]  
  • Diamonti, A. J., Guy, P. M., Ivanof, C., Wong, K., Sweeney, C., Carraway, K. L. III (2002). An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. Proc. Natl. Acad. Sci. USA 10.1073/pnas.052709799v1 [Abstract] [Full Text]  
  • Yamaguchi, A., Taniguchi, M., Hori, O., Ogawa, S., Tojo, N., Matsuoka, N., Miyake, S.-i., Kasai, K., Sugimoto, H., Tamatani, M., Yamashita, T., Tohyama, M. (2002). Peg3/Pw1 Is Involved in p53-mediated Cell Death Pathway in Brain Ischemia/Hypoxia. J. Biol. Chem. 277: 623-629 [Abstract] [Full Text]  
  • Susini, L., Passer, B. J., Amzallag-Elbaz, N., Juven-Gershon, T., Prieur, S., Privat, N., Tuynder, M., Gendron, M.-C., Israel, A., Amson, R., Oren, M., Telerman, A. (2001). Siah-1 binds and regulates the function of Numb. Proc. Natl. Acad. Sci. USA 98: 15067-15072 [Abstract] [Full Text]  
  • Suzuki, Y., Nakabayashi, Y., Takahashi, R. (2001). Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc. Natl. Acad. Sci. USA 10.1073/pnas.161506698v1 [Abstract] [Full Text]  
  • Parkinson, J., Everett, R. D. (2000). Alphaherpesvirus Proteins Related to Herpes Simplex Virus Type 1 ICP0 Affect Cellular Structures and Proteins. J. Virol. 74: 10006-10017 [Abstract] [Full Text]  
  • Aguilera, M., Oliveros, M., Martínez-Padrón, M., Barbas, J. A., Ferrús, A. (2000). Ariadne-1: A Vital Drosophila Gene Is Required in Development and Defines a New Conserved Family of RING-Finger Proteins. Genetics 155: 1231-1244 [Abstract] [Full Text]  
  • Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H., Weissman, A. M. (2000). Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53. J. Biol. Chem. 275: 8945-8951 [Abstract] [Full Text]  
  • Zhang, H., Xu, Q., Krajewski, S., Krajewska, M., Xie, Z., Fuess, S., Kitada, S., Godzik, A., Reed, J. C. (2000). BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins. Proc. Natl. Acad. Sci. USA 97: 2597-2602 [Abstract] [Full Text]  
  • Lehembre, F., Badenhorst, P., Müller, S., Travers, A., Schweisguth, F., Dejean, A. (2000). Covalent Modification of the Transcriptional Repressor Tramtrack by the Ubiquitin-Related Protein Smt3 in Drosophila Flies. Mol. Cell. Biol. 20: 1072-1082 [Abstract] [Full Text]  
  • Ota, S., Hazeki, K., Rao, N., Lupher, M. L. Jr., Andoniou, C. E., Druker, B., Band, H. (2000). The RING Finger Domain of Cbl Is Essential for Negative Regulation of the Syk Tyrosine Kinase. J. Biol. Chem. 275: 414-422 [Abstract] [Full Text]  
  • Wilkinson, K. D. (1999). Ubiquitin-Dependent Signaling: The Role of Ubiquitination in the Response of Cells to Their Environment.. J. Nutr. 129: 1933-1936 [Abstract] [Full Text]  
  • Yokouchi, M., Kondo, T., Houghton, A., Bartkiewicz, M., Horne, W. C., Zhang, H., Yoshimura, A., Baron, R. (1999). Ligand-induced Ubiquitination of the Epidermal Growth Factor Receptor Involves the Interaction of the c-Cbl RING Finger and UbcH7. J. Biol. Chem. 274: 31707-31712 [Abstract] [Full Text]  
  • Moynihan, T. P., Ardley, H. C., Nuber, U., Rose, S. A., Jones, P. F., Markham, A. F., Scheffner, M., Robinson, P. A. (1999). The Ubiquitin-conjugating Enzymes UbcH7 and UbcH8 Interact with RING Finger/IBR Motif-containing Domains of HHARI and H7-AP1. J. Biol. Chem. 274: 30963-30968 [Abstract] [Full Text]  
  • Lorick, K. L., Jensen, J. P., Fang, S., Ong, A. M., Hatakeyama, S., Weissman, A. M. (1999). RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl. Acad. Sci. USA 96: 11364-11369 [Abstract] [Full Text]  
  • Waterman, H., Levkowitz, G., Alroy, I., Yarden, Y. (1999). The RING Finger of c-Cbl Mediates Desensitization of the Epidermal Growth Factor Receptor. J. Biol. Chem. 274: 22151-22154 [Abstract] [Full Text]  
  • Roperch, J.-P., Lethrone, F., Prieur, S., Piouffre, L., Israeli, D., Tuynder, M., Nemani, M., Pasturaud, P., Gendron, M.-C., Dausset, J., Oren, M., Amson, R. B., Telerman, A. (1999). SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: Identification of common effectors with p53 and p21Waf1. Proc. Natl. Acad. Sci. USA 96: 8070-8073 [Abstract] [Full Text]  
  • Seol, J. H., Feldman, R.M. R., Zachariae, W., Shevchenko, A., Correll, C. C., Lyapina, S., Chi, Y., Galova, M., Claypool, J., Sandmeyer, S., Nasmyth, K., Shevchenko, A., Deshaies, R. J. (1999). Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev. 13: 1614-1626 [Abstract] [Full Text]  
  • Tanikawa, J., Ichikawa-Iwata, E., Kanei-Ishii, C., Nakai, A., Matsuzawa, S.-i., Reed, J. C., Ishii, S. (2000). p53 Suppresses the c-Myb-induced Activation of Heat Shock Transcription Factor 3. J. Biol. Chem. 275: 15578-15585 [Abstract] [Full Text]  
  • Moriwaki, Y., Begum, N. A., Kobayashi, M., Matsumoto, M., Toyoshima, K., Seya, T. (2001). Mycobacterium bovis Bacillus Calmette-Guerin and Its Cell Wall Complex Induce a Novel Lysosomal Membrane Protein, SIMPLE, That Bridges the Missing Link between Lipopolysaccharide and p53-inducible Gene, LITAF(PIG7), and Estrogen-inducible Gene, EET-1. J. Biol. Chem. 276: 23065-23076 [Abstract] [Full Text]  
  • Ettenberg, S. A., Magnifico, A., Cuello, M., Nau, M. M., Rubinstein, Y. R., Yarden, Y., Weissman, A. M., Lipkowitz, S. (2001). Cbl-b-dependent Coordinated Degradation of the Epidermal Growth Factor Receptor Signaling Complex. J. Biol. Chem. 276: 27677-27684 [Abstract] [Full Text]  
  • Diamonti, A. J., Guy, P. M., Ivanof, C., Wong, K., Sweeney, C., Carraway, K. L. III (2002). An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. Proc. Natl. Acad. Sci. USA 99: 2866-2871 [Abstract] [Full Text]  
  • Suzuki, Y., Nakabayashi, Y., Takahashi, R. (2001). Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc. Natl. Acad. Sci. USA 98: 8662-8667 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»