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.

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

PANDOLFI DE RINALDIS, Pier Paolo;
2005-01-01

Abstract

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.
2005
105
292
300
http://dx.doi.org/10.1182/blood-2004-03-1185
Active Transport; Cell Nucleus; Amino Acid Sequence; Animals; Binding Sites; Cell Differentiation; Cell Line; Tumor; 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
L. A. Nguyen;P. P. Pandolfi;Y. Aikawa;Y. Tagata;M. Ohki;I. Kitabayashi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/64259
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