THE BMI-1 ONCOPROTEIN INTERACTS WITH DING AND MPH2 - THE ROLE OF RINGFINGER DOMAINS

Experimentally-induced mutations in the C3HC4 RING finger domain of th e 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-pr otein interactions is examined using the yeast two-hybrid system. Bmi- 1 interacts directly with the RING finger protein dinG/RING1B. Heterod imerization of the two proteins requires the intact RING finger struct ures of both Bmi-1 and dinG. Although the RING finger domains are nece ssary for dimerization, they are not sufficient for this process as re sidues outside the C3HC4 motif are also required. Thus, binding specif icity may be partly conferred by residues outside the RING motif. Both Bmi-1 and dinG interact with the Polyhomeotic protein MPh2 through bi nding domains apart from the RING finger. The data suggest a model whe reby Bmi-1, dinG, and MPh2 form a stable heterotrimeric complex in whi ch each protein contributes to the binding of the others.