Hemenway C S, Halligan B W, Levy L S
Department of Pediatrics, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Oncogene. 1998 May 14;16(19):2541-7. doi: 10.1038/sj.onc.1202042.
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.
实验诱导的Bmi-1癌蛋白C3HC4型锌指结构域突变会阻碍其在小鼠体内诱导淋巴瘤的能力。在本报告中，利用酵母双杂交系统研究了Bmi-1锌指在介导蛋白质-蛋白质相互作用中的作用。Bmi-1直接与锌指蛋白dinG/RING1B相互作用。两种蛋白质的异源二聚化需要Bmi-1和dinG两者完整的锌指结构。虽然锌指结构域对于二聚化是必需的，但它们对于这个过程并不充分，因为C3HC4基序之外的残基也是必需的。因此，结合特异性可能部分由锌指基序之外的残基赋予。Bmi-1和dinG都通过除锌指之外的结合结构域与多同源蛋白MPh2相互作用。数据表明了一种模型，即Bmi-1、dinG和MPh2形成一个稳定的异源三聚体复合物，其中每种蛋白质都有助于其他蛋白质的结合。
