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首页> 外文期刊>Chinese science bulletin >Oligomerization study of NHR3 and NHR4 domains from ETO protein involved in t(8;21)-associated acute myeloid leukemia
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Oligomerization study of NHR3 and NHR4 domains from ETO protein involved in t(8;21)-associated acute myeloid leukemia

机译：ETO蛋白参与与t（8; 21）相关的急性髓细胞白血病的NHR3和NHR4结构域的寡聚研究

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摘要

Little had been known about ETO protein until t(8;21) was found in 12 percent-15 percent of acute myeloid leukemia which resulted in AML1-ETG fusion protein. ETO protein has four conserved nervy homology regions termed NHR1 - 4. A lot have already been known about NHR1,2,4: NHR1 is homologous with the Drosophila TATA-box-associated factor 110 (TAF110); NHR2 is a dimerization domain associated with mSin3A/HDAC; NHR4 is MYND class of zinc fingers associated with NCoR/SMRT/HDAC. Only the function of NHR3 remains unclear. In order to- investigate whether NHR3 domain could participate in oligomerization, we cloned and purified this domain. Through gel filtration chromatography, dynamic light scattering and dissolved crystal electrophoresis, we found that NHR3 domain was a tight tetramer. Then we cloned NHM3+4 domain (i.e. NHR3 domain plus NHR4 domain), and discovered, by gel filtration chromatography and native PAGE, that NHR3+4 domain could form dimer in solution. This was the first time to observe that NHR3 and NHR4 domains may have some contribution to the oligomerization of ETO protein, which might recruit corepressors in the form of dimer, and stabilize ETO dimerization through convergent strength of NHR2, NHR3 and NHR4 domains and then stabilize corepressors recruitment. These speculations are very worthy of further evaluation.
机译：关于ETO蛋白知之甚少，直到在12％-15％的急性髓性白血病中发现t（8; 21），从而导致AML1-ETG融合蛋白。 ETO蛋白具有四个保守的神经同源性区域，称为NHR1-4。NHR1,2,4已为人们所知：NHR1与果蝇TATA盒相关因子110（TAF110）同源; NHR2是与mSin3A / HDAC相关的二聚化域; NHR4是与NCoR / SMRT / HDAC相关的MYND类锌指。仅NHR3的功能尚不清楚。为了研究NHR3结构域是否可以参与寡聚，我们克隆并纯化了该结构域。通过凝胶过滤色谱，动态光散射和溶解晶体电泳，我们发现NHR3域是紧密的四聚体。然后我们克隆了NHM3 + 4结构域（即NHR3结构域和NHR4结构域），并通过凝胶过滤色谱和天然PAGE发现NHR3 + 4结构域可以在溶液中形成二聚体。这是首次观察到NHR3和NHR4结构域可能对ETO蛋白的寡聚化有一些贡献，它可能以二聚体的形式募集共加压子，并通过NHR2，NHR3和NHR4结构域的聚合强度稳定ETO二聚化，然后稳定corepressors招聘。这些推测非常值得进一步评估。

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