Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.
Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.
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DOI：
10.1182/blood.v96.7.2557.h8002557_2557_2561
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发表时间：
2000-10
期刊：
影响因子：
20.3
通讯作者：
F. Guidez;Kevin Petrie;A. Ford;Huafeng Lu;Caroline A. Bennett;Angus J. MacGregor;J. Hannemann;Yoshiaki Ito;J. Ghysdael;Mel F. Greaves;Leanne M. Wiedemann;A. Zelent
中科院分区：
文献类型：
--
作者：
F. Guidez;Kevin Petrie;A. Ford;Huafeng Lu;Caroline A. Bennett;Angus J. MacGregor;J. Hannemann;Yoshiaki Ito;J. Ghysdael;Mel F. Greaves;Leanne M. Wiedemann;A. Zelent
t（12; 21）（p13; q22）染色体易位是儿科癌症中最常见的非法基因重组，并且发生在约25%的常见急性淋巴细胞白血病（cALL）病例中。这种重排导致ETS相关基因TEL（ETV 6）的5 ′-区与几乎整个急性髓性白血病1（AML 1）（也称为CBFA 2或PEBP 2AB 1）基因座的框内融合和TEL-AML 1嵌合蛋白的表达。虽然AML 1刺激转录，但TEL-AML 1作为一些AML 1靶基因的阻遏物发挥作用。与野生型AML 1蛋白相反，TEL和TEL-AML 1都与N-CoR相互作用，N-CoR是具有组蛋白脱乙酰酶活性的核受体辅阻遏物复合物的组分。TEL和N-CoR之间的相互作用需要TEL的中心区域，该区域保留在TEL-AML 1中，并且缺少该结构域的TEL在转录抑制中受损。总之，我们的研究结果表明，TEL-AML 1可能有助于通过招募N-CoR到AML 1靶基因，从而改变其表达模式的白血病发生。
The t(12;21)(p13;q22) chromosomal translocation is the most frequent illegitimate gene recombination in a pediatric cancer and occurs in approximately 25% of common acute lymphoblastic leukemia (cALL) cases. This rearrangement results in the in frame fusion of the 5'-region of the ETS-related gene, TEL (ETV6), to almost the entire acute myeloid leukemia 1 (AML1) (also called CBFA2 or PEBP2AB1) locus and expression of the TEL-AML1 chimeric protein. Although AML1 stimulates transcription, TEL-AML1 functions as a repressor of some AML1 target genes. In contrast to the wild type AML1 protein, both TEL and TEL-AML1 interact with N-CoR, a component of the nuclear receptor corepressor complex with histone deacetylase activity. The interaction between TEL and N-CoR requires the central region of TEL, which is retained in TEL-AML1, and TEL lacking this domain is impaired in transcriptional repression. Taken together, our results suggest that TEL-AML1 may contribute to leukemogenesis by recruiting N-CoR to AML1 target genes and thus imposing an altered pattern of their expression.