The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING finger domains
The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING finger domains
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DOI：
10.1038/sj.onc.1202042
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发表时间：
1998-05-14
期刊：
影响因子：
8
通讯作者：
Levy, LS
中科院分区：
文献类型：
--
作者：
Hemenway, CS;Halligan, BW;Levy, LS
实验诱导的Bmi-1癌蛋白C3 HC 4环指结构域突变阻断了其诱导小鼠淋巴瘤的能力。在本报告中，使用酵母双杂交系统研究了Bmi-1 RING指在介导蛋白质-蛋白质相互作用中的作用。Bmi-1与RING指蛋白dinG/RING 1B直接相互作用。这两种蛋白质的异源二聚化需要Bmi-1和dinG的完整RING指结构。尽管RING指结构域对于二聚化是必需的，但是它们对于该过程是不够的，因为还需要C3 HC 4基序之外的残基。因此，结合特异性可能部分由RING基序外的残基赋予。Bmi-1和dinG都通过除了RING指之外的结合结构域与多同源异型蛋白MPh 2相互作用。这些数据表明，Bmi-1，dinG和MPh 2形成一个稳定的异源三聚体复合物，其中每个蛋白质有助于其他蛋白质的结合模型。
Experimentally-induced mutations in the C3HC4 RING finger domain of the Bmi-1 oncoprotein block its ability to induce lymphomas in mice. In this report, the role of the Bmi-1 RING finger in mediating protein-protein interactions is examined using the yeast two-hybrid system. Bmi-1 interacts directly with the RING finger protein dinG/RING1B. Heterodimerization of the two proteins requires the intact RING finger structures of both Bmi-1 and dinG. Although the RING finger domains are necessary for dimerization, they are not sufficient for this process as residues outside the C3HC4 motif are also required. Thus, binding specificity may be partly conferred by residues outside the RING motif. Both Bmi-1 and dinG interact with the Polyhomeotic protein MPh2 through binding domains apart from the RING finger. The data suggest a model whereby Bmi-1, dinG, and MPh2 form a stable heterotrimeric complex in which each protein contributes to the binding of the others.