Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;16)

Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence o...

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Veröffentlicht in:Oncogene 2000-11, Vol.19 (50), p.5821-5825
Hauptverfasser: HOSAKA, Taisuke, KANOE, Hiroshi, NAKAMURA, Takashi, TOGUCHIDA, Junya, NAKAYAMA, Tomitaka, MURAKAMI, Hiroshi, YAMAMOTO, Hiroshi, NAKAMATA, Takeharu, TSUBOYAMA, Tadao, OKA, Masanori, KASAI, Masataka, SASAKI, Masao S
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container_end_page 5825
container_issue 50
container_start_page 5821
container_title Oncogene
container_volume 19
creator HOSAKA, Taisuke
KANOE, Hiroshi
NAKAMURA, Takashi
TOGUCHIDA, Junya
NAKAYAMA, Tomitaka
MURAKAMI, Hiroshi
YAMAMOTO, Hiroshi
NAKAMATA, Takeharu
TSUBOYAMA, Tadao
OKA, Masanori
KASAI, Masataka
SASAKI, Masao S
description Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (>70%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding affinity of each motif showed considerable differences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. Considering the high incidence and specific binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas.
doi_str_mv 10.1038/sj.onc.1203943
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The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. 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We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (&gt;70%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding affinity of each motif showed considerable differences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. Considering the high incidence and specific binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>11126370</pmid><doi>10.1038/sj.onc.1203943</doi><tpages>5</tpages></addata></record>
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source MEDLINE; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings
subjects Binding Sites
Biological and medical sciences
Bone surgery
Breakpoints
CCAAT-Enhancer-Binding Proteins - genetics
Cell interactions, adhesion
CHOP gene
chromosome 12
chromosome 16
Chromosome Breakage
Chromosome translocations
Chromosomes
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 16
Consensus Sequence
DNA binding proteins
DNA, Neoplasm - genetics
DNA, Neoplasm - metabolism
DNA-Binding Proteins - metabolism
Electrophoretic mobility
fibrosarcoma
Fundamental and applied biological sciences. Psychology
Fusion protein
Genes
Genetic aspects
HeLa Cells
Humans
Leukemia
liposarcoma
Liposarcoma, Myxoid - genetics
Liposarcoma, Myxoid - metabolism
Molecular and cellular biology
Oligonucleotides
Oligonucleotides - genetics
Oligonucleotides - metabolism
Oncogene Proteins, Fusion - genetics
Orthopedics
Physiological aspects
Proteins
Risk factors
RNA-Binding Protein FUS
Sarcoma
Substrate Specificity
TLS gene
Transcription Factor CHOP
translin
Translocation (Genetics)
Translocation, Genetic
TSN protein
Tumors
title Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;16)
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