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

Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8756-61. doi: 10.1073/pnas.121433898. Epub 2001 Jul 3.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Gene Fusion
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Cell Transformation, Neoplastic
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9*
  • DNA, Complementary
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fatty Acid-Binding Proteins
  • Histone-Lysine N-Methyltransferase
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Infant
  • Leukemia, Myelomonocytic, Acute / genetics
  • Leukemia, Myelomonocytic, Acute / metabolism*
  • Leukemia, Myelomonocytic, Acute / pathology
  • Male
  • Molecular Sequence Data
  • Myeloid-Lymphoid Leukemia Protein
  • Proto-Oncogenes*
  • Tissue Distribution
  • Transcription Factors*
  • Vesicular Transport Proteins*

Substances

  • Carrier Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • FNBP1 protein, human
  • Fatty Acid-Binding Proteins
  • KMT2A protein, human
  • Transcription Factors
  • Vesicular Transport Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase

Associated data

  • GENBANK/AF265550