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The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia

Item Type:Article
Title:The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia
Creators Name:Fuchs, U. and Rehkamp, G. and Haas, O.A. and Slany, R. and Konig, M. and Bojesen, S. and Bohle, R.M. and Damm-Welk, C. and Ludwig, W.D. and Harbott, J. and Borkhardt, A.
Abstract:We have cloned a fusion partner of the MLL gene at 11q23 and identified it as the gene encoding the human formin-binding protein 17, FBP17. It maps to chromosome 9q34 centromeric to ABL. The gene fusion results from a complex chromosome rearrangement that was resolved by fluorescence in situ hybridization with various probes on chromosomes 9 and 11 as an ins(11;9)(q23;q34)inv(11)(q13q23). The rearrangement resulted in a 5'-MLL/FBP17-3' fusion mRNA. We retrovirally transduced murine-myeloid progenitor cells with MLL/FBP17 to test its transforming ability. In contrast to MLL/ENL, MLL/ELL and other MLL-fusion genes, MLL/FBP17 did not give a positive readout in a serial replating assay. Therefore, we assume that additional cooperating genetic abnormalities might be needed to establish a full malignant phenotype. FBP17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in Schizosaccharomyces pombe. Both domains are separated by a consensus Rho-binding motif that has been identified in different Rho-interaction partners such as Rhotekin and Rhophilin. We evaluated whether FBP17 and members of the Rho family interact in vivo with a yeast two-hybrid assay. None of the various Rho proteins tested, however, interacted with FBP17. We screened a human kidney library and identified a sorting nexin, SNX2, as a protein interaction partner of FBP17. These data provide a link between the epidermal growth factor receptor pathway and an MLL fusion protein.
Keywords:Artificial Gene Fusion, Base Sequence, Carrier Proteins, Cell Nucleus, Neoplastic Cell Transformation, Chromosome Mapping, Human Chromosomes Pair 9, Complementary DNA, DNA-Binding Proteins, Fluorescence In Situ Hybridization, Acute Myelomonocytic Leukemia, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein, Proto-Oncogenes, Tissue Distribution, Transcription Factors, Vesicular Transport Proteins
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:8756-8761
Date:17 July 2001
Official Publication:https://doi.org/10.1073/pnas.121433898
PubMed:View item in PubMed

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