The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16;21)-positive myeloid malignancies
The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16;21)-positive myeloid malignancies
复制标题
DOI：
10.1038/sj.onc.1205882
复制
发表时间：
2002-09-26
期刊：
影响因子：
8
通讯作者：
Sacchi, N
中科院分区：
文献类型：
--
作者：
Hoogeveen, AT;Rossetti, S;Sacchi, N
MTG（Myeloid Translocation Gene）蛋白是一类新的转录辅抑制因子。我们报告MTG 16 a，一种由骨髓恶性肿瘤中t（16; 21）紊乱的MTG 16基因编码的蛋白质亚型，靶向于核仁。核仁定位所需的氨基酸序列被映射到MTG 16 a的N-末端区域。MTG 16 a与MTG 8一样，是一种被t（8; 21）扰乱的核辅阻遏物，能够与特定的组蛋白脱乙酰酶（HDAC）相互作用，表明该蛋白可能介导核仁基因转录的沉默。此外，MTG 16 a能够与其他MTG蛋白形成寡聚体。作为t（16; 21）的结果，AML 1 DNA结合结构域取代了MTG 16 a N-末端区域。AML 1-MTG 16融合蛋白靶向核质，在那里它能够与MTG 16 a寡聚化并与HDAC 1和HDAC 3相互作用。在t（16; 21）髓系恶性肿瘤的发病机制中，核仁部位含有HDAC的复合物的缺乏和AML 1部位含有HDAC的复合物的积累可能是关键的。
The MTG (Myeloid Translocation Gene) proteins are a family of novel transcriptional corepressors. We report that MTG16a, a protein isoform encoded by the MTG16 gene deranged by the t (16; 21) in myeloid malignancies, is targeted to the nucleolus. The amino acid sequence necessary for nucleolar localization was mapped to the MTG16a N-terminal region. MTG16a, like MTG8, the nuclear corepressor deranged by the t (8; 21), is capable to interact with specific histone deacetylases (HDACs) suggesting that the protein may mediate silencing of nucleolar gene transcription. In addition, MTG16a is capable to form oligomers with other MTG proteins. As a consequence of the t (16; 21) the AML1 DNA-binding domain replaces the MTG16a N-terminal region. The AML1-MTG16 fusion protein is targeted to the nucleoplasm where it is capable to oligomerize with MTG16a and interact with HDAC1 and HDAC3. The deficiency of HDAC-containing complexes at nucleolar sites and the accumulation of HDAC-containing complexes at AML1-sites may be critical in the pathogenesis of t (16; 21) myeloid malignancies.