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Titolo:
GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24)
Autore:
Eguchi, M; Eguchi-Ishimae, M; Seto, M; Morishita, K; Suzuki, K; Ueda, R; Ueda, K; Kamada, N; Greaves, M;
Indirizzi:
Inst Canc Res, Leukaemia Res Fund Ctr, Chester Beatty Labs, London SW3 6JB, England Inst Canc Res London England SW3 6JB eatty Labs, London SW3 6JB, England Aichi Canc Ctr, Res Inst, Mol Med Lab, Nagoya, Aichi 464, Japan Aichi CancCtr Nagoya Aichi Japan 464 l Med Lab, Nagoya, Aichi 464, Japan Miyazaki Med Coll, Dept Biochem, Miyazaki 88916, Japan Miyazaki Med Coll Miyazaki Japan 88916 pt Biochem, Miyazaki 88916, Japan Kinki Univ, Sch Engn, Dept Chem & Environm Technol, Hiroshima, Japan KinkiUniv Hiroshima Japan pt Chem & Environm Technol, Hiroshima, Japan Nagoya Univ, Sch Med, Dept Internal Med 1, Nagoya, Aichi 466, Japan NagoyaUniv Nagoya Aichi Japan 466 ternal Med 1, Nagoya, Aichi 466, Japan Hiroshima Univ, Sch Med, Dept Pediat, Hiroshima, Japan Hiroshima Univ Hiroshima Japan , Sch Med, Dept Pediat, Hiroshima, Japan Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Canc Cytogenet, Hiroshima, Japan Hiroshima Univ Hiroshima Japan d, Dept Canc Cytogenet, Hiroshima, Japan
Titolo Testata:
GENES CHROMOSOMES & CANCER
fascicolo: 3, volume: 32, anno: 2001,
pagine: 212 - 221
SICI:
1045-2257(200111)32:3<212:GANPGF>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BREAKPOINT CLUSTER REGION; DNA TOPOISOMERASE-II; TAU-PROTEIN; MICROTUBULE-BINDING; CHROMOSOME TRANSLOCATIONS; HOMOLOGOUS RECOMBINATION; INFANT LEUKEMIA; SELF-FUSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Eguchi, M Inst Canc Res, Leukaemia Res Fund Ctr, Chester Beatty Labs, 237 Fulham Rd,London SW3 6JB, England Inst Canc Res 237 Fulham Rd London England SW3 6JB 6JB, England
Citazione:
M. Eguchi et al., "GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24)", GENE CHROM, 32(3), 2001, pp. 212-221

Abstract

We report a novel MLL-associated chromosome translocation t(11;14)(q23;q24) in a child who showed signs of acute undifferentiated leukemia 3 years after intensive chemotherapy, that included the topoisomerase-II inhibitor VP16. Screening of a cDNA library of the patient's leukemic cells showed a novel fusion transcript between MLL and the Gephyrin (GPHN) gene on 14q24. The resulting MLL-GPHN fusion gene encodes MLL AT hook motifs and a DNA methyltransferase homology domain fused to the C-terminal half of Gephyrin, including a presumed tubulin binding site and a domain homologous to the Escherichia coli molybdenum cofactor biosynthesis protein MoeA. Genomic breakpoint analysis showed potential, in vitro topoisomerase-II DNA-binding sites spanning the breakpoints in both MLL and GPHN but no flanking sequences thatmight mediate homologous recombination. This suggests that MLL-GPHN may have been generated by VP 16/topoisomerase-II-induced DNA double-strand breaks, followed by error-prone DNA repair via non-homologous end joining. Gephyrin was originally identified as a submembraneous scaffold protein that anchors and immobilizes postsynaptic membrane neurotransmitter receptors to underlying cytoskeletal elements. It also is reported to bind to phosphatidylinositol 3,4,5-triphosphate binding proteins involved in actin dynamics anddownstream signaling and, interacts with ATM-related family member RAFTI. Gephyrin domains in the chimeric protein therefore could contribute novel signal sequences or might modify MLL activity by oligomerization or intracellular redistribution. (C) 2001 Wiley-Liss, Inc.

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Documento generato il 30/03/20 alle ore 20:09:10