The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in t(9;11)(p22;q23) acute leukemias.
Polycomb group (PcG) proteins assemble to form large multiprotein complexes involved in gene silencing. Evidence suggests that PcG complexes are heterogeneous with respect to both protein composition and specific function. MPc3 is a recently described mouse Polycomb (Pc) protein that shares structural homology with at least two other Pc proteins, M33 and MPc2. All three Pc proteins bind another PcG protein, RING1, through a conserved carboxy-terminal C-box motif. Here, data are presented demonstrating that MPc3 also interacts with AF9, a transcriptional activator implicated in the development of acute leukemias. The carboxy-terminus of AF9 is fused to the MLL protein in leukemias characterized by t(9;11)(p22;q23) chromosomal translocations. Importantly, it is the carboxy-terminus of AF9 to which MPc3 binds. The AF9 binding site of MPc3 maps to a central, non-conserved, region of the polypeptide sequence. In contrast to MPc3, data indicate that the Pc protein M33 does not interact with AF9. This finding suggests a potentially unique role for MPc3 in linking a PcG silencing complex to a transcriptional activator protein.
Hemenway
C S
CS
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, LA 70112, USA. chemenw@tulane.edu
de Erkenez
A C
AC
Gould
G C
GC
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000378:metabolism*; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011233:Precipitin Tests; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014178:Translocation, Genetic; D020798:Two-Hybrid System Techniques
C570426:Cbx2 protein, mouse; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C489901:MLLT3 protein, human; D033681:Mitochondrial Membrane Transport Proteins; C489902:Mllt3 protein, mouse; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D063146:Polycomb-Group Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; C570429:Cbx8 protein, mouse; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human; C489840:Ring1 protein, mouse