title: Identification and characterization of OSTL (RNF217) encoding a RING-IBR-RING protein adjacent to a translocation breakpoint involving ETV6 in childhood ALL.
abstract: Genomic aberrations involving ETV6 on band 12p13 are amongst the most common chromosomal abnormalities in human leukemia. The translocation t(6;12)(q23;13) in a childhood B-cell acute lymphoblastic leukemia (ALL) cell line fuses ETV6 with the putative long non-coding RNA gene STL. Linking STL properties to leukemia has so far been difficult. Here, we describe a novel gene, OSTL (annotated as RNF217 in Genbank), which shares the first exon and a CpG island with STL but is transcribed in the opposite direction. Human RNF217 codes for a highly conserved RING finger protein and is mainly expressed in testis and skeletal muscle with different splice variants. RNF217 shows regulated splicing in B cell development, and is expressed in a number of human B cell leukemia cell lines, primary human chronic myeloid leukemia, acute myeloid leukemia with normal karyotype and acute T-ALL samples. Using a yeast two-hybrid screen, we identified the anti-apoptotic protein HAX1 to interact with RNF217. This interaction could be mapped to the C-terminal RING finger motif of RNF217. We propose that some of the recurring aberrations involving 6q might deregulate the expression of RNF217 and result in imbalanced apoptosis signalling via HAX1, promoting leukemia development.
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians-Universität, Munich (LMU), Germany.
authors.forename: Luciana M
authors.initials: LM
authors.lastname: Fontanari Krause
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians-Universität, Munich (LMU), Germany.
authors.forename: Anna Sophia
authors.initials: AS
authors.lastname: Japp
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians-Universität, Munich (LMU), Germany.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krause
authors.affiliation: Laboratory for Molecular Stem Cell Biology, Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Mooster
authors.affiliation: Faculty of Medical and Health Sciences, Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand.
authors.forename: Martin
authors.initials: M
authors.lastname: Chopra
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Müschen
authors.affiliation: 1] Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians-Universität, Munich (LMU), Germany [2] Faculty of Medical and Health Sciences, Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D018899:CpG Islands / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D017434:Protein Structure, Tertiary; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020033:Protein Isoforms; D050783:Proto-Oncogene Proteins c-ets; D062085:RNA, Long Noncoding; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C104759:HAX1 protein, human; C000602435:RNF217 protein, human