Identification and characterization of OSTL (RNF217) encoding a RING-IBR-RING protein adjacent to a translocation breakpoint involving ETV6 in childhood ALL.
Identification and characterization of OSTL (RNF217) encoding a RING-IBR-RING protein adjacent to a translocation breakpoint involving ETV6 in childhood ALL.
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DOI：
10.1038/srep06565
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发表时间：
2014-10-09
影响因子：
4.6
通讯作者：
Bohlander SK
中科院分区：
文献类型：
--
作者：
Fontanari Krause LM;Japp AS;Krause A;Mooster J;Chopra M;Müschen M;Bohlander SK
基因组畸变涉及ETV 6在带12 p13是人类白血病中最常见的染色体异常之一。易位t（6; 12）（q23; 13）在儿童B细胞急性淋巴细胞白血病（ALL）细胞系中融合ETV 6与推定的长非编码RNA基因STL。到目前为止，将STL属性与白血病联系起来还很困难。在这里，我们描述了一个新的基因，OSTL（在Genbank中注释为RNF 217），它与STL共享第一个外显子和一个CpG岛，但转录方向相反。人RNF 217编码高度保守的RING指蛋白，主要表达于睾丸和骨骼肌中，具有不同的剪接变体。RNF 217在B细胞发育中显示出受调节的剪接，并且在许多人B细胞白血病细胞系、原发性人慢性髓性白血病、具有正常核型的急性髓性白血病和急性T-ALL样品中表达。使用酵母双杂交筛选，我们确定了抗凋亡蛋白HAX 1与RNF 217相互作用。这种相互作用可以映射到RNF 217的C-末端RING指基序。我们认为，一些涉及6 q的复发性异常可能会失调RNF 217的表达，并导致通过HAX 1的细胞凋亡信号传导失衡，从而促进白血病的发展。
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.
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DOI：
10.1016/j.bbrc.2010.02.084
发表时间：
2010-03-19
影响因子：
3.1
作者：
Kang, Young Ji;Jang, Mi;Park, Sung Goo
通讯作者：
Park, Sung Goo
影响因子：
11.4
作者：
Jadayel, DM;Lukas, J;Catovsky, D
通讯作者：
Catovsky, D
影响因子：
--
作者：
Li B;Hu Q;Xu R;Ren H;Fei E;Chen D;Wang G
通讯作者：
Wang G
影响因子：
8
作者：
Greif, P. A.;Tizazu, B.;Bohlander, S. K.
通讯作者：
Bohlander, S. K.
DOI：
10.1159/000056818
发表时间：
2000-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Bohlander, SK
通讯作者：
Bohlander, SK