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 Kitabayashi, I.
Right arrow Articles by Ohki, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kitabayashi, I.
Right arrow Articles by Ohki, M.

 Previous Article  |  Next Article 

Mol Cell Biol, February 1998, p. 846-858, Vol. 18, No. 2
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The AML1-MTG8 Leukemic Fusion Protein Forms a Complex with a Novel Member of the MTG8(ETO/CDR) Family, MTGR1

Issay Kitabayashi,1,* Kohmei Ida,1 Fumiko Morohoshi,1 Akihiko Yokoyama,1 Naoko Mitsuhashi,1 Kimiko Shimizu,1 Nobuo Nomura,2 Yasuhide Hayashi,3 and Misao Ohki1

Radiobiology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104,1 Kazusa DNA Research Institute, Kisarazu, Chiba 292,2 and Department of Pediatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113,3 Japan

Received 18 August 1997/Returned for modification 6 October 1997/Accepted 9 November 1997

The AML1-CBFbeta transcription factor complex is essential for the definitive hematopoiesis of all lineages and is the most frequent target of chromosomal rearrangements in human leukemia. In the t(8;21) translocation associated with acute myeloid leukemia (AML), the AML1(CBFA2/PEBP2alpha B) gene is juxtaposed to the MTG8(ETO/CDR) gene. We show here that the resultant AML1-MTG8 gene product specifically and strongly interacts with an 85-kDa phosphoprotein. Molecular cloning of cDNA indicated that the AML1-MTG8-binding protein (MTGR1) is highly related to MTG8 and similar to Drosophila Nervy. Comparison of amino acid sequences among MTGR1, MTG8, and Nervy revealed four evolutionarily conserved regions (NHR1 to NHR4). Ectopic expression of AML1-MTG8 in L-G murine myeloid progenitor cells inhibits differentiation to mature neutrophils and induces cell proliferation in response to granulocyte colony-stimulating factor (G-CSF). Analysis with C-terminal deletion mutants of AML1-MTG8 indicated that the region of 51 residues (488 to 538), which contains NHR2, is essential for the induction of G-CSF-dependent cell proliferation. Immunoprecipitation analysis indicates that this region is required for AML1-MTG8 to form a stable complex with MTGR1. Overexpression of MTGR1 stimulates AML1-MTG8 to induce G-CSF-dependent proliferation of L-G cells and to interfere with AML1-dependent transcription. These results suggest that AML1-MTG8 could function as a complex with MTGR1 and that the complex might be important in promoting leukemogenesis.

* Corresponding author. Mailing address: Radiobiology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan. Phone: 81-3-3542-2511, ext. 4751. Fax: 81-3-3542-0688. E-mail: ikitabay{at}ncc.go.jp.




This article has been cited by other articles:

  • DE BRAEKELEER, E., FEREC, C., DE BRAEKELEER, M. (2009). RUNX1 Translocations in Malignant Hemopathies. Anticancer Res 29: 1031-1037 [Abstract] [Full Text]  
  • Roudaia, L., Cheney, M. D., Manuylova, E., Chen, W., Morrow, M., Park, S., Lee, C.-T., Kaur, P., Williams, O., Bushweller, J. H., Speck, N. A. (2009). CBF{beta} is critical for AML1-ETO and TEL-AML1 activity. Blood 113: 3070-3079 [Abstract] [Full Text]  
  • Chyla, B. J., Moreno-Miralles, I., Steapleton, M. A., Thompson, M. A., Bhaskara, S., Engel, M., Hiebert, S. W. (2008). Deletion of Mtg16, a Target of t(16;21), Alters Hematopoietic Progenitor Cell Proliferation and Lineage Allocation. Mol. Cell. Biol. 28: 6234-6247 [Abstract] [Full Text]  
  • Kumar, R., Cheney, K. M., McKirdy, R., Neilsen, P. M., Schulz, R. B., Lee, J., Cohen, J., Booker, G. W., Callen, D. F. (2008). CBFA2T3-ZNF652 Corepressor Complex Regulates Transcription of the E-box Gene HEB. J. Biol. Chem. 283: 19026-19038 [Abstract] [Full Text]  
  • Moore, A. C., Amann, J. M., Williams, C. S., Tahinci, E., Farmer, T. E., Martinez, J. A., Yang, G., Luce, K. S., Lee, E., Hiebert, S. W. (2008). Myeloid Translocation Gene Family Members Associate with T-Cell Factors (TCFs) and Influence TCF-Dependent Transcription. Mol. Cell. Biol. 28: 977-987 [Abstract] [Full Text]  
  • Kumar, R., Manning, J., Spendlove, H. E., Kremmidiotis, G., McKirdy, R., Lee, J., Millband, D. N., Cheney, K. M., Stampfer, M. R., Dwivedi, P. P., Morris, H. A., Callen, D. F. (2006). ZNF652, A Novel Zinc Finger Protein, Interacts with the Putative Breast Tumor Suppressor CBFA2T3 to Repress Transcription. Mol Cancer Res 4: 655-665 [Abstract] [Full Text]  
  • Amann, J. M., Chyla, B. J. I., Ellis, T. C., Martinez, A., Moore, A. C., Franklin, J. L., McGhee, L., Meyers, S., Ohm, J. E., Luce, K. S., Ouelette, A. J., Washington, M. K., Thompson, M. A., King, D., Gautam, S., Coffey, R. J., Whitehead, R. H., Hiebert, S. W. (2005). Mtgr1 Is a Transcriptional Corepressor That Is Required for Maintenance of the Secretory Cell Lineage in the Small Intestine. Mol. Cell. Biol. 25: 9576-9585 [Abstract] [Full Text]  
  • Frohling, S., Scholl, C., Gilliland, D. G., Levine, R. L. (2005). Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications. JCO 23: 6285-6295 [Abstract] [Full Text]  
  • Sledz, C. A., Williams, B. R. G. (2005). RNA interference in biology and disease. Blood 106: 787-794 [Abstract] [Full Text]  
  • Liu, S., Shen, T., Huynh, L., Klisovic, M. I., Rush, L. J., Ford, J. L., Yu, J., Becknell, B., Li, Y., Liu, C., Vukosavljevic, T., Whitman, S. P., Chang, K.-S., Byrd, J. C., Perrotti, D., Plass, C., Marcucci, G. (2005). Interplay of RUNX1/MTG8 and DNA Methyltransferase 1 in Acute Myeloid Leukemia. Cancer Res. 65: 1277-1284 [Abstract] [Full Text]  
  • Nguyen, L. A., Pandolfi, P. P., Aikawa, Y., Tagata, Y., Ohki, M., Kitabayashi, I. (2005). Physical and functional link of the leukemia-associated factors AML1 and PML. Blood 105: 292-300 [Abstract] [Full Text]  
  • Yan, M., Burel, S. A., Peterson, L. F., Kanbe, E., Iwasaki, H., Boyapati, A., Hines, R., Akashi, K., Zhang, D.-E. (2004). From the Cover: Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development. Proc. Natl. Acad. Sci. USA 101: 17186-17191 [Abstract] [Full Text]  
  • Lausen, J., Cho, S., Liu, S., Werner, M. H. (2004). The Nuclear Receptor Co-repressor (N-CoR) Utilizes Repression Domains I and III for Interaction and Co-repression with ETO. J. Biol. Chem. 279: 49281-49288 [Abstract] [Full Text]  
  • Zhang, J., Kalkum, M., Yamamura, S., Chait, B. T., Roeder, R. G. (2004). E Protein Silencing by the Leukemogenic AML1-ETO Fusion Protein. Science 305: 1286-1289 [Abstract] [Full Text]  
  • Ibanez, V., Sharma, A., Buonamici, S., Verma, A., Kalakonda, S., Wang, J., Kadkol, S., Saunthararajah, Y. (2004). AML1-ETO Decreases ETO-2 (MTG16) Interactions with Nuclear Receptor Corepressor, an Effect That Impairs Granulocyte Differentiation. Cancer Res. 64: 4547-4554 [Abstract] [Full Text]  
  • Chevallier, N., Corcoran, C. M., Lennon, C., Hyjek, E., Chadburn, A., Bardwell, V. J., Licht, J. D., Melnick, A. (2004). ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cell lymphoma oncoprotein. Blood 103: 1454-1463 [Abstract] [Full Text]  
  • Mulloy, J. C., Cammenga, J., Berguido, F. J., Wu, K., Zhou, P., Comenzo, R. L., Jhanwar, S., Moore, M. A. S., Nimer, S. D. (2003). Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element. Blood 102: 4369-4376 [Abstract] [Full Text]  
  • Barseguian, K., Lutterbach, B., Hiebert, S. W., Nickerson, J., Lian, J. B., Stein, J. L., van Wijnen, A. J., Stein, G. S. (2002). Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins. Proc. Natl. Acad. Sci. USA 99: 15434-15439 [Abstract] [Full Text]  
  • Yokoyama, A., Kitabayashi, I., Ayton, P. M., Cleary, M. L., Ohki, M. (2002). Leukemia proto-oncoprotein MLL is proteolytically processed into 2 fragments with opposite transcriptional properties. Blood 100: 3710-3718 [Abstract] [Full Text]  
  • Schwieger, M., Lohler, J., Friel, J., Scheller, M., Horak, I., Stocking, C. (2002). AML1-ETO Inhibits Maturation of Multiple Lymphohematopoietic Lineages and Induces Myeloblast Transformation in Synergy with ICSBP Deficiency. JEM 196: 1227-1240 [Abstract] [Full Text]  
  • Hug, B. A., Lee, S. Y. D., Kinsler, E. L., Zhang, J., Lazar, M. A. (2002). Cooperative Function of Aml1-ETO Corepressor Recruitment Domains in the Expansion of Primary Bone Marrow Cells. Cancer Res. 62: 2906-2912 [Abstract] [Full Text]  
  • Schillace, R. V., Andrews, S. F., Liberty, G. A., Davey, M. P., Carr, D. W. (2002). Identification and Characterization of Myeloid Translocation Gene 16b as a Novel A Kinase Anchoring Protein in T Lymphocytes. J. Immunol. 168: 1590-1599 [Abstract] [Full Text]  
  • Michaud, J., Wu, F., Osato, M., Cottles, G. M., Yanagida, M., Asou, N., Shigesada, K., Ito, Y., Benson, K. F., Raskind, W. H., Rossier, C., Antonarakis, S. E., Israels, S., McNicol, A., Weiss, H., Horwitz, M., Scott, H. S. (2002). In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Blood 99: 1364-1372 [Abstract] [Full Text]  
  • Mulloy, J. C., Cammenga, J., MacKenzie, K. L., Berguido, F. J., Moore, M. A. S., Nimer, S. D. (2002). The AML1-ETO fusion protein promotes the expansion of human hematopoietic stem cells. Blood 99: 15-23 [Abstract] [Full Text]  
  • Amann, J. M., Nip, J., Strom, D. K., Lutterbach, B., Harada, H., Lenny, N., Downing, J. R., Meyers, S., Hiebert, S. W. (2001). ETO, a Target of t(8;21) in Acute Leukemia, Makes Distinct Contacts with Multiple Histone Deacetylases and Binds mSin3A through Its Oligomerization Domain. Mol. Cell. Biol. 21: 6470-6483 [Abstract] [Full Text]  
  • Burel, S. A., Harakawa, N., Zhou, L., Pabst, T., Tenen, D. G., Zhang, D.-E. (2001). Dichotomy of AML1-ETO Functions: Growth Arrest versus Block of Differentiation. Mol. Cell. Biol. 21: 5577-5590 [Abstract] [Full Text]  
  • Calabi, F., Pannell, R., Pavloska, G. (2001). Gene Targeting Reveals a Crucial Role for MTG8 in the Gut. Mol. Cell. Biol. 21: 5658-5666 [Abstract] [Full Text]  
  • Zhang, J., Hug, B. A., Huang, E. Y., Chen, C. W., Gelmetti, V., Maccarana, M., Minucci, S., Pelicci, P. G., Lazar, M. A. (2001). Oligomerization of ETO Is Obligatory for Corepressor Interaction. Mol. Cell. Biol. 21: 156-163 [Abstract] [Full Text]  
  • Bruserud, O., Gjertsen, B. T., Huang, T.-s. (2000). Induction of Differentiation and Apoptosis-- A Possible Strategy in the Treatment of Adult Acute Myelogenous Leukemia. The Oncologist 5: 454-462 [Abstract] [Full Text]  
  • Wood, J. D., Nucifora, F. C. Jr., Duan, K., Zhang, C., Wang, J., Kim, Y., Schilling, G., Sacchi, N., Liu, J. M., Ross, C. A. (2000). Atrophin-1, the Dentato-Rubral and Pallido-Luysian Atrophy Gene Product, Interacts with Eto/Mtg8 in the Nuclear Matrix and Represses Transcription. JCB 150: 939-948 [Abstract] [Full Text]  
  • Shimada, H., Ichikawa, H., Nakamura, S., Katsu, R., Iwasa, M., Kitabayashi, I., Ohki, M. (2000). Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF. Blood 96: 655-663 [Abstract] [Full Text]  
  • Shimizu, K., Kitabayashi, I., Kamada, N., Abe, T., Maseki, N., Suzukawa, K., Ohki, M. (2000). AML1-MTG8 leukemic protein induces the expression of granulocyte colony-stimulating factor (G-CSF) receptor through the up-regulation of CCAAT/enhancer binding protein epsilon. Blood 96: 288-296 [Abstract] [Full Text]  
  • Melnick, A. M., Westendorf, J. J., Polinger, A., Carlile, G. W., Arai, S., Ball, H. J., Lutterbach, B., Hiebert, S. W., Licht, J. D. (2000). The ETO Protein Disrupted in t(8;21)-Associated Acute Myeloid Leukemia Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein. Mol. Cell. Biol. 20: 2075-2086 [Abstract] [Full Text]  
  • McNeil, S., Zeng, C., Harrington, K. S., Hiebert, S., Lian, J. B., Stein, J. L., van Wijnen, A. J., Stein, G. S. (1999). The t(8;21) chromosomal translocation in acute myelogenous leukemia modifies intranuclear targeting of the AML1/CBFalpha 2 transcription factor. Proc. Natl. Acad. Sci. USA 96: 14882-14887 [Abstract] [Full Text]  
  • Ichikawa, H., Shimizu, K., Katsu, R., Ohki, M. (1999). Dual Transforming Activities of the FUS (TLS)-ERG Leukemia Fusion Protein Conferred by Two N-Terminal Domains of FUS (TLS). Mol. Cell. Biol. 19: 7639-7650 [Abstract] [Full Text]  
  • Michelson, R. J., Collard, M. W., Ziemba, A. J., Persinger, J., Bartholomew, B., Huggenvik, J. I. (1999). Nuclear DEAF-1-related (NUDR) Protein Contains a Novel DNA Binding Domain and Represses Transcription of the Heterogeneous Nuclear Ribonucleoprotein A2/B1 Promoter. J. Biol. Chem. 274: 30510-30519 [Abstract] [Full Text]  
  • Kasper, L. H., Brindle, P. K., Schnabel, C. A., Pritchard, C. E. J., Cleary, M. L., van Deursen, J. M. A. (1999). CREB Binding Protein Interacts with Nucleoporin-Specific FG Repeats That Activate Transcription and Mediate NUP98-HOXA9 Oncogenicity. Mol. Cell. Biol. 19: 764-776 [Abstract] [Full Text]  
  • Lutterbach, B., Westendorf, J. J., Linggi, B., Patten, A., Moniwa, M., Davie, J. R., Huynh, K. D., Bardwell, V. J., Lavinsky, R. M., Rosenfeld, M. G., Glass, C., Seto, E., Hiebert, S. W. (1998). ETO, a Target of t(8;21) in Acute Leukemia, Interacts with the N-CoR and mSin3 Corepressors. Mol. Cell. Biol. 18: 7176-7184 [Abstract] [Full Text]  
  • Gelmetti, V., Zhang, J., Fanelli, M., Minucci, S., Pelicci, P. G., Lazar, M. A. (1998). Aberrant Recruitment of the Nuclear Receptor Corepressor-Histone Deacetylase Complex by the Acute Myeloid Leukemia Fusion Partner ETO. Mol. Cell. Biol. 18: 7185-7191 [Abstract] [Full Text]  
  • Fracchiolla, N. S., Colombo, G., Finelli, P., Maiolo, A. T., Neri, A. (1998). EHT, a New Member of the MTG8/ETO Gene Family, Maps on 20q11 Region and Is Deleted in Acute Myeloid Leukemias. Blood 92: 3481-3484 [Full Text]  
  • Lutterbach, B., Sun, D., Schuetz, J., Hiebert, S. W. (1998). The MYND Motif Is Required for Repression of Basal Transcription from the Multidrug Resistance 1 Promoter by the t(8;21) Fusion Protein. Mol. Cell. Biol. 18: 3604-3611 [Abstract] [Full Text]  
  • Gamou, T., Kitamura, E., Hosoda, F., Shimizu, K., Shinohara, K., Hayashi, Y., Nagase, T., Yokoyama, Y., Ohki, M. (1998). The Partner Gene of AML1 in t(16;21) Myeloid Malignancies Is a Novel Member of the MTG8(ETO) Family. Blood 91: 4028-4037 [Abstract] [Full Text]  
  • Jakubowiak, A., Pouponnot, C., Berguido, F., Frank, R., Mao, S., Massague, J., Nimer, S. D. (2000). Inhibition of the Transforming Growth Factor beta 1 Signaling Pathway by the AML1/ETO Leukemia-associated Fusion Protein. J. Biol. Chem. 275: 40282-40287 [Abstract] [Full Text]  
  • Hildebrand, D., Tiefenbach, J., Heinzel, T., Grez, M., Maurer, A. B. (2001). Multiple Regions of ETO Cooperate in Transcriptional Repression. J. Biol. Chem. 276: 9889-9895 [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»