Functional contribution of EEN to leukemogenic transformation by MLL-EEN fusion protein.
The EEN (extra eleven nineteen) gene was originally cloned from a case of acute myeloid leukemia M5 subtype with translocation t (11; 19)(q23; p13), in which EEN was fused with MLL. To explore the involvement of EEN in leukemogenesis caused by MLL-EEN, we studied the transformation potential of the MLL-EEN fusion protein. MLL-EEN had oncogenic features, while, as a control, MLLDelta, the truncated form of MLL lacking the EEN moiety, did not show any oncogenic potential. MLL-EEN exerted a dominant-negative effect over wild-type EEN in terms of subcellular localization. Normally, EEN was found in the cytoplasm, but the MLL-EEN fusion protein was located in the nucleus, and EEN could be delocalized by MLL-EEN. This interaction is via a coiled-coil dimerization domain of EEN, which is reserved in the fusion protein. In addition, MLL-EEN might act as a potential transcriptional factor with the MLL part providing the DNA-binding domain and the EEN part providing the transcription activation domain, though EEN seems to have no direct role in transcriptional regulation. As an aberrant transcriptional factor, MLL-EEN could transactivate the promoter of HoxA7, a potential target gene of MLL.
Liu
Han
H
State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital affiliated to Shanghai Second Medical University, 197 Ruijin Road II, Shanghai 200025, PR China.
Chen
Bing
B
Xiong
Hui
H
Huang
Qiu-Hua
QH
Zhang
Qing-Hua
QH
Wang
Zhu-Gang
ZG
Li
Bo-Liang
BL
Chen
Zhu
Z
Chen
Sai-Juan
SJ
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D019281:Dimerization; D018922:HL-60 Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007938:Leukemia / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation
D002352:Carrier Proteins; C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; C492047:Hoxa7 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C482572:MLL-EEN fusion protein, human; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; C105159:SH3GL1 protein, human; D051788:Myeloid-Lymphoid Leukemia Protein