MLL fusion partners AF4 and AF9 interact at subnuclear foci.
The MLL gene is involved in translocations associated with both acute lymphoblastic and acute myelogenous leukemia. These translocations fuse MLL with one of over 30 partner genes. Collectively, the MLL partner genes do not share a common structural motif or biochemical function. We have identified a protein interaction between the two most common MLL fusion partners AF4 and AF9. This interaction is restricted to discrete nuclear foci we have named 'AF4 bodies'. The AF4 body is non-nucleolar and is not coincident with any known nuclear structures we have examined. The AF4-AF9 interaction is maintained by the MLL-AF4 fusion protein, and expression of the MLL-AF4 fusion can alter the subnuclear localization of AF9. In view of other research indicating that other MLL fusion partners also interact with one another, these results suggest that MLL fusion partners may participate in a web of protein interactions with a common functional goal. The disruption of this web of interactions by fusion with MLL may be important to leukemogenesis.
Erfurth
F
F
Department of Pathology, The University of Chicago, Chicago, IL, USA. ferfurt@lumc.edu
Hemenway
C S
CS
de Erkenez
A C
AC
Domer
P H
PH
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D011519:Proto-Oncogenes; D012441:Saccharomyces cerevisiae; D013347:Subcellular Fractions; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C113855:MLL-AF4 fusion protein, human; C474558:MLL-AF9 fusion protein, human; C489901:MLLT3 protein, human; D009363:Neoplasm Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D011495:Histone-Lysine N-Methyltransferase; D005982:Glutathione Transferase