The ENL moiety of the childhood leukemia-associated MLL–ENL oncoprotein recruits human Polycomb 3

@article{GarcaCullar2001TheEM,
  title={The ENL moiety of the childhood leukemia-associated MLL–ENL oncoprotein recruits human Polycomb 3},
  author={M-P Garc{\'i}a-Cu{\'e}llar and Olaf Zilles and Silke Schreiner and Marco T. Birke and Thomas H. Winkler and Robert K Slany},
  journal={Oncogene},
  year={2001},
  volume={20},
  pages={411-419}
}
The translocation t(11;19) is frequently found in acute leukemia in infants. This event truncates the proto-oncogene MLL and fuses the 5′ end of MLL in frame with the ENL gene. ENL contributes a crucial protein–protein interaction domain to the resulting oncoprotein MLL–ENL. Here we show by yeast two-hybrid assays, GST-pull-down experiments and in a far western blot analysis that this domain is necessary and sufficient to recruit a novel member of the human Polycomb protein family (hPc3). hPc3… Expand
The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin
TLDR
A direct interaction between several nuclear MLL fusion partners is demonstrated and evidence for a role of these proteins in histone binding is presented, supporting a common role for nuclear M LL fusion partners in chromatin biology. Expand
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TLDR
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TLDR
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TLDR
A function of ENL in histone modification and transcriptional elongation is suggested, according to structure-function data, which suggests DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. Expand
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TLDR
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Chromosomal translocations that fuse the mixed lineage leukemia gene (MLL) to a variety of unrelated partner genes are frequent in pediatric leukemias. The novel combination of genetic material leadsExpand
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TLDR
It is shown that chromobox homolog 8 (CBX8), a Polycomb Group protein that interacts with MLL-AF9 and TIP60, is required for MLL -AF9-induced transcriptional activation and leukemogenesis and Surprisingly, Cbx8-deficient mice are viable and display no apparent hematopoietic defects. Expand
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ENL, the MLL fusion partner in t(11;19), binds to the c-Abl interactor protein 1 (ABI1) that is fused to MLL in t(10;11)+
TLDR
It is shown here that the frequent MLL fusion partner ENL at 19p13.1 interacts with the human homologue of the mouse Abl-Interactor 1 (ABI1) protein, which is fused to MLL in the t(10;11)(p11.2;q23) translocation. Expand
The leukemogenic fusion of MLL with ENL creates a novel transcriptional transactivator
TLDR
It is shown here that the fusion of MLL with ENL creates a novel molecule that is a potent general transcriptional transactivator in transient reporter gene assays and the ENL C-terminus as a binding partner for an unknown factor and the MLL MT region as a unique general DNA binding motif. Expand
ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells.
TLDR
The leukemogenic contribution and transcriptional activation potential of Enl colocalize to its highly conserved carboxy terminus, suggesting that Hrx-Enl chimeric proteins mediate alterations in the transcription program of t(11;19)-bearing cells. Expand
The Oncogenic Capacity of HRX-ENL Requires the Transcriptional Transactivation Activity of ENL and the DNA Binding Motifs of HRX
TLDR
These studies support a model in which HRX-ENL induces myeloid transformation by deregulating subordinate genes through a gain of function contributed by the transcriptional effector properties of ENL. Expand
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TLDR
It is found that ETO, through its interaction with the N-CoR/mSin3/HDAC1 complex, is also a potent repressor of transcription, providing a mechanism for how the AML1/ETO fusion may inhibit expression of AML 1-responsive target genes and disturb normal hematopoiesis. Expand
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TLDR
A novel role for a trithorax-homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites is suggested, implicated to play an important role in bacterial IHF, yeast datin-, and mammalian HMG-mediated gene activation. Expand
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TLDR
A direct role for HRX–ENL is demonstrated in the immortalization and leukemic transformation of a myeloid progenitor and a gain‐of‐function mechanism for HRZ‐ENL‐mediated leukemogenesis is supported. Expand
Interference with the expression of a novel human polycomb protein, hPc2, results in cellular transformation and apoptosis
TLDR
The data suggest that hPc2 is a repressor of proto-oncogene activity and that interference with hP C-terminal domain function can lead to derepression of Proto- oncogene transcription and subsequently to cellular transformation. Expand
THE AML1‐ETO CHIMAERIC TRANSCRIPTION FACTOR IN ACUTE MYELOID LEUKAEMIA: BIOLOGY AND CLINICAL SIGNIFICANCE
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TLDR
The understanding of the normal function of AML1/CBFb in haemopoiesis is summarized, and the mechanism through which t(8;21) induces leukaemia is described. Expand
The Mll–AF9 gene fusion in mice controls myeloproliferation and specifies acute myeloid leukaemogenesis
TLDR
The late onset of overt tumours suggests that secondary tumorigenic mutations are necessary for malignancy associated with MLL–AF9 gene fusion and that myeloproliferation provides the pool of cells in which such events can occur. Expand
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