Physical and functional link of the leukemia-associated factors AML1 and PML.

The AML1-CBFbeta transcription factor complex is the most frequent target of specific chromosome translocations in acute myeloid leukemia (AML). The promyelocytic leukemia (PML) gene is also frequently involved in AML-associated translocation. Here we report that a specific isoform PML I forms a complex with AML1. PML I was able to ...
recruit AML1 and coactivator p300 in PML nuclear bodies and enhance the AML1-mediated transcription in the presence of p300. A specific C-terminal region of PML I and a C-terminal region of AML1 were found to be required for both their association and colocalization in the nuclear bodies. Overexpression of PML I stimulates myeloid cells to differentiate. These results suggest that PML I could act as a mediator for AML1 and its coactivator p300/CBP to assemble into functional complexes and, consequently, activate AML1-dependent transcription and myeloid cell differentiation.
Mesh Terms:
Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, Binding Sites, Cell Differentiation, Cell Line, Tumor, Cell Nucleus, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, E1A-Associated p300 Protein, Gene Expression Regulation, Neoplastic, Granulocyte Colony-Stimulating Factor, Humans, Leukemia, Mice, Molecular Sequence Data, Myeloid Cells, Neoplasm Proteins, Nuclear Proteins, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Proto-Oncogene Proteins, Sequence Alignment, Signal Transduction, Trans-Activators, Transcription Factors, Tumor Suppressor Proteins
Blood
Date: Jan. 01, 2005
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