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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1445-1453. Prepublished online as a Blood First Edition Paper on October 9, 2003; DOI 10.1182/blood-2003-07-2452. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2452v1 103/4/1445    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yam, J. W. P. Articles by Chan, L. C. Search for Related Content PubMed PubMed Citation Articles by Yam, J. W. P. Articles by Chan, L. C. Related Collections Oncogenes and Tumor Suppressors Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Identification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein Judy Wai Ping Yam, Dong-Yan Jin, Chi Wai So, and Li Chong Chan From the Department of Pathology and Department of Biochemistry, The University of Hong Kong; and Department of Pathology, Stanford University, Palo Alto, CA. The chimeric MLL-EEN fusion protein is created as a result of chromosomal translocation t(11;19)(q23;p13). EEN, an Src homology 3 (SH3) domain–containing protein in the endophilin family, has been implicated in endocytosis, although little is known about its role in leukemogenesis mediated by the MLL-EEN fusion protein. In this study, we have identified and characterized EBP, a novel EEN binding protein that interacts with the SH3 domain of EEN through a proline-rich motif PPERP. EBP is a ubiquitous protein that is normally expressed in the cytoplasm but is recruited to the nucleus by MLL-EEN with a punctate localization pattern characteristic of the MLL chimeric proteins. EBP interacts simultaneously with EEN and Sos, a guanine-nucleotide exchange factor for Ras. Coexpressoin of EBP with EEN leads to suppression of Ras-induced cellular transformation and Ras-mediated activation of Elk-1. Taken together, our findings suggest a new mechanism for MLL-EEN–mediated leukemogenesis in which MLL-EEN interferes with the Ras-suppressing activities of EBP through direct interaction. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H.-Y. Le, Y. Zhang, H. Liu, L.-H. Ma, Y. Jin, Q.-H. Huang, Y. Chen, M. Deng, Z. Chen, S.-J. Chen, et al. eena Promotes Myeloid Proliferation through Stimulating ERK1/2 Phosphorylation in Zebrafish J. Biol. Chem., June 20, 2008; 283(25): 17652 - 17661. [Abstract] [Full Text] [PDF] L.-H. Ma, H. Liu, H. Xiong, B. Chen, X.-W. Zhang, Y.-Y. Wang, H.-Y. Le, Q.-H. Huang, Q.-H. Zhang, B.-L. Li, et al. Aberrant transcriptional regulation of the MLL fusion partner EEN by AML1-ETO and its implication in leukemogenesis Blood, January 15, 2007; 109(2): 769 - 777. [Abstract] [Full Text] [PDF] J. W. P. Yam, F. C. F. Ko, C.-Y. Chan, D.-Y. Jin, and I. O.-L. Ng Interaction of Deleted in Liver Cancer 1 with Tensin2 in Caveolae and Implications in Tumor Suppression. Cancer Res., September 1, 2006; 66(17): 8367 - 8372. [Abstract] [Full Text] [PDF] B. L. Lua and B. C. Low Activation of EGF receptor endocytosis and ERK1/2 signaling by BPGAP1 requires direct interaction with EEN/endophilin II and a functional RhoGAP domain J. Cell Sci., June 15, 2005; 118(12): 2707 - 2721. [Abstract] [Full Text] [PDF]

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