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

Hosaka, Taisuke; Kanoe, Hiroshi; Nakayama, Tomitaka; Murakami, Hiroshi; Yamamoto, Hiroshi; Nakamata, Takeharu; Tsuboyama, Tadao; Oka, M.; Kasai, Masataka; Sasaki, Masao S.; Nakamura, Takashi; Toguchida, Junya

doi:10.1038/sj.onc.1203943

Cited by 29 publications

(19 citation statements)

References 16 publications

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“…In two tumors (cases 2 and 3), the breakpoint sequence showed strong homology to the consensus binding site sequence of Translin. Translin is a protein involved in recombination and translocations, as it not only binds to translocation breakpoint sequences in hematopoietic malignancies but also binds to translocation breakpoints in alveolar rhabdomyosarcomas and liposarcomas (Aoki et al, 1995;Chalk et al, 1997;Hosaka et al, 2000). The degress of homology to consensus Translin-binding sites observed in this study (71 and 75%, respectively) was in accordance to those reported previously in liposarcomas (more than 70%), but higher than those reported in alveolar rhabdomyosarcomas (62%).…”

Section: Discussionsupporting

confidence: 81%

“…The positions of other recombination sequences (heptamer/nonamer, chi consensus, alternating purine/pyrimidine, polypurine or polypyrimidine sequences) were not correlated with those of the junction points. However, using criteria similar to Hosaka et al (2000), we found that the sense sequence at the SYT breakpoint in tumor 3 and the antisense sequence at the SSX1 breakpoint in tumor 2 (Figure 3) had a strong homology (71 and 75%, respectively) to the consensus recognition sequences of Translin.…”

Section: Resultsmentioning

confidence: 99%

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Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

et al. 2003

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The SYT-SSXI and SYT-SSX2 fusion genes, derived by reciprocal translocations t(X;18), are acquired genetic events strongly associated with the tumorigenesis of synovial sarcoma. In approaching the mechanisms underlying the formation of these fusion oncogenes, we have analysed the genomic sequences surrounding the SYT-SSX breakpoints in 10 tumors, two expressing SYT-SSXI and eight expressing SYT-SSX2 fusion transcripts. The breakpoints were found to be clustered in the 5 0 end of intron 10 of SYT, and in two cluster regions within intron 4 of SSX2, whereas the two breakpoints in SSX1 intron 4 were 0.5 kb apart. SYT intron 10 is abundant in repetitive regions with the interspersed repeats occupying 66% of the whole intron. Nine of the 10 breakpoints in intron 10 of SYT and six of the eight breakpoints in intron 4 of SSX2 were at or near repetitive regions. These findings suggest that repetitive regions may contribute to the distribution of genomic breakpoints. Several of the fusion sequences exhibited characteristic signs of nonhomologous end joining, including microhomologies at the end points as well as deletions. Sequences highly homologous (83-94%) to consensus topoisomerase II cleavage sites were identified at or near the breakpoints in all 10 tumors, suggesting a role of this enzyme in creating staggered ends at the breakpoint. Furthermore, sequences highly homologous to consensus Translin binding sequences were found at the breakpoints in two cases, and an Alu-Alu fusion and an insertion of a 206-bp LINE-1 element were found at the breakpoint in one case each. The demonstration of characteristic sequences at the SYT-SSX breakpoint regions is expected to improve our understanding of the molecular genetic mechanisms behind translocations in general, and of the SYT-SSX fusions in synovial sarcoma in particular.

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Section: Discussionsupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

et al. 2003

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confidence: 98%

“…For example, translin binding sites at, or close to, the breakpoint junctions have been found in the neoplasia-related t(1; 14)(p32;q11), t(2;13)(q35;q14), t(8;14)(q24;q11), t(12;16)(q13;p11), and t(14;18)(q32;q21) (Aoki et al, 1995;Chalk et al, 1997;Kanoe et al, 1999;Hosaka et al, 2000). However, such sequences are very frequent in the human genome (Hosaka et al, 2000), and the presence of binding motifs close to breakpoint junctions may well be fortuitous. Enzymes have also been implicated, with binding sites for DNA topoisomerases I and II having been identified in inv(10)(q11q11) in thyroid carcinomas (Klugbauer et al, 2001) and in t(9;11)(p22;q23) in therapy-related AML (Felix et al, 1995;Atlas et al, 1998), respectively.…”

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confidence: 98%

Genomic characterization of MOZ/CBP and CBP/MOZ chimeras in acute myeloid leukemia suggests the involvement of a damage‐repair mechanism in the origin of the t(8;16)(p11;p13)

Panagopoulos

Isaksson

Hagemeijer³

et al. 2002

Genes Chromosomes & Cancer

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The t(8;16)(p11;p13), which is strongly associated with acute myeloid leukemia (AML) displaying monocytic differentiation, erythrophagocytosis by the leukemic cells, and a poor response to chemotherapy, fuses the MOZ gene (8p11) with the CBP gene (16p13). Although genomic rearrangements of MOZ and CBP have been detected using fluorescence in situ hybridization and Southern blot analyses, characterization of the breakpoints at the sequence level has never been performed. We have sequenced the breakpoints in four t(8;16)-positive AML cases with the aim to identify molecular genetic mechanisms underlying the origin of this translocation. In addition, an exon/intron map of the MOZ gene was constructed, which was found to be composed of 17 exons. Long-range-PCR with CBP forward primers in exon 2 and MOZ reverse primers in exon 17 as well as with a MOZ forward primer in exon 16 and a CBP reverse primer in intron 2 successfully amplified CBP/MOZ and MOZ/CBP hybrid genomic DNA fragments in all four AMLs. The breaks clustered in both CBP intron 2 and MOZ intron 16, and were close to repetitive elements, and in one case an Alu-Alu junction for the CBP/MOZ hybrid was identified. Additional genomic events (i.e., deletions, duplications, and insertions) in the breakpoint regions in both the MOZ and CBP genes were found in all four cases. Thus, the t(8;16) does not originate through a simple end-to-end fusion. The findings of multiple breaks and rearrangements rather suggest the involvement of a damage-repair mechanism in the origin of this translocation.

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“…It is intriguing that neither the PKA-nor the PKC-mediated signaling pathway contributes to this rescue effect of the A 2A -R. Instead, a novel A 2A -R-interacting protein [the Translin-associated protein X (TRAX) (Aoki et al, 1997)] that binds to the C terminus of the A 2A -R might mediate the rescue effect of A 2A -R. TRAX was originally identified as a binding protein of Translin using a yeast two-hybrid system (Aoki et al, 1997). Translin is a protein that binds RNA and singlestranded DNA with potential functions in DNA rearrangement and repair, mitotic cell division, mRNA transport, and translational regulation (Aoki et al, 1995(Aoki et al, , 1997Han et al, 1995;Wu et al, 1997;Hosaka et al, 2000;Ishida et al, 2002;Yang et al, 2003). TRAX is a 33-kDa protein whose amino acids have 28% identity to those of Translin (Aoki et al, 1997).…”

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confidence: 99%

Rescue of p53 Blockage by the A2A Adenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X

Sun¹,

Cheng²,

Chou³

et al. 2006

Molecular Pharmacology

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Blockage of the p53 tumor suppressor has been found to impair nerve growth factor (NGF)-induced neurite outgrowth in PC-12 cells. We report herein that such impairment could be rescued by stimulation of the A 2A adenosine receptor (A 2A -R), a G protein-coupled receptor implicated in neuronal plasticity. The A 2A -R-mediated rescue occurred in the presence of protein kinase C (PKC) inhibitors or protein kinase A (PKA) inhibitors and in a PKA-deficient PC-12 variant. Thus, neither PKA nor PKC was involved. In contrast, expression of a truncated A 2A -R mutant harboring the seventh transmembrane domain and its C terminus reduced the rescue effect of A 2A -R. Using the cytoplasmic tail of the A 2A -R as bait, a novel-A 2A -R-interacting protein [translin-associated protein X (TRAX)] was identified in a yeast two-hybrid screen. The authenticity of this interaction was verified by pull-down experiments, coimmunoprecipitation, and colocalization of these two molecules in the brain. It is noteworthy that reduction of TRAX using an antisense construct suppressed the rescue effect of A 2A -R, whereas overexpression of TRAX alone caused the same rescue effect as did A 2A -R activation. Results of [ 3 H]thymidine and bromodeoxyuridine incorporation suggested that A 2A -R stimulation inhibited cell proliferation in a TRAX-dependent manner. Because the antimitotic activity is crucial for NGF function, the A 2A -R might exert its rescue effect through a TRAX-mediated antiproliferative signal. This antimitotic activity of the A 2A -R also enables a mitogenic factor (epidermal growth factor) to induce neurite outgrowth. We demonstrate that the A 2A -R modulates the differentiation ability of trophic factors through a novel interacting protein, TRAX.

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

Cited by 29 publications

References 16 publications

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

Characteristic sequence motifs located at the genomic breakpoints of the translocation t(X;18) in synovial sarcomas

Genomic characterization of MOZ/CBP and CBP/MOZ chimeras in acute myeloid leukemia suggests the involvement of a damage‐repair mechanism in the origin of the t(8;16)(p11;p13)

Rescue of p53 Blockage by the A2A Adenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X

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