The Bmi-1 oncoprotein interacts with dinG and MPh2: the role of RING finger domains.
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.
Hemenway
C S
CS
Department of Pediatrics, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Halligan
B W
BW
Levy
L S
LS
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012097:Repressor Proteins; D013329:Structure-Activity Relationship; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers / Q000502:physiology*
C069077:BMI1 protein, human; C489421:Bmi1 protein, mouse; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D009698:Nucleoproteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C072820:ph-d protein, Drosophila; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human; C489841:RNF2 protein, human; C489840:Ring1 protein, mouse; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases