title: The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia.
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.
authors: Department of Pediatric Hematology and Oncology, University of Giessen, 35392 Giessen, Germany.
authors: U
authors: U
authors: Fuchs
authors: G
authors: G
authors: Rehkamp
authors: O A
authors: OA
authors: Haas
authors: R
authors: R
authors: Slany
authors: M
authors: M
authors: Kōnig
authors: S
authors: S
authors: Bojesen
authors: R M
authors: RM
authors: Bohle
authors: C
authors: C
authors: Damm-Welk
authors: W D
authors: WD
authors: Ludwig
authors: J
authors: J
authors: Harbott
authors: A
authors: A
authors: Borkhardt
mesh_terms: D019677:Artificial Gene Fusion; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D014018:Tissue Distribution; D014157:Transcription Factors; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C433770:FNBP1 protein, human; D050556:Fatty Acid-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase