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PMID: 11438682 Published · ppublish English Case Reports Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 15 ·2001-07-17 ·Pages 8756-61

Fuchs U, Rehkamp G, Haas OA, Slany R, Kōnig M, Bojesen S, Bohle RM, Damm-Welk C, Ludwig WD, Harbott J, 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.

MeSH Terms
Artificial Gene Fusion Base Sequence Carrier Proteins/genetics,metabolism Cell Nucleus/metabolism Cell Transformation, Neoplastic Chromosome Mapping Chromosomes, Human, Pair 9 DNA, Complementary DNA-Binding Proteins/genetics,metabolism Fatty Acid-Binding Proteins Histone-Lysine N-Methyltransferase Humans In Situ Hybridization, Fluorescence/methods Infant Leukemia, Myelomonocytic, Acute/genetics,metabolism,pathology Male Molecular Sequence Data Myeloid-Lymphoid Leukemia Protein Proto-Oncogenes Tissue Distribution Transcription Factors Vesicular Transport Proteins
Chemicals
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
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Fuchs U
Department of Pediatric Hematology and Oncology, University of Giessen, 35392 Giessen, Germany.
Rehkamp G
Haas O A
Slany R
Kōnig M
Bojesen S
Bohle R M
Damm-Welk C
Ludwig W D
Harbott J
Borkhardt A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.121433898
Published
2001-07-17
Epub
2001-00-03
Pages
8756-61
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC37508
Subset
IM
Databases
GENBANK
AF265550
External Links
PubMed source DOI: 10.1073/pnas.121433898 PMC Full Text View journal details
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