The MN1-TEL myeloid leukemia-associated fusion protein has a dominant-negative effect on RAR-RXR-mediated transcription
Copyright policy )The MN1-TEL myeloid leukemia-associated fusion protein has a dominant-negative effect on RAR-RXR-mediated transcription
The translocation t(12;22)(p13;q11) creates an MN1-TEL fusion gene leading to acute myeloid leukemia. MN1 is a transcription coactivator of the retinoic acid and vitamin D receptors, and TEL (ETV6) is a member of the E26-transformation-specific family of transcription factors. In MN1-TEL, the transactivating domains of MN1 are combined with the DNA-binding domain of TEL. We show that MN1-TEL inhibits retinoic acid receptor (RAR)-mediated transcription, counteracts coactivators such as p160 and p300, and acts as a dominant-negative mutant of MN1. Compared to MN1, the same transactivation domains in MN1-TEL are poorly stimulated by p160, p300 or histone deacetylase inhibitors, indicating that the block of RAR-mediated transcription by MN1-TEL is caused by dysfunctional transactivation domains rather than by recruitment of corepressors. The mechanism leading to myeloid leukemia in t(12;22) thus differs from the translocations that involve RAR itself.
- Erasmus University Rotterdam Netherlands
- Spanish National Research Council Spain
- St. Jude Children's Research Hospital United States
- National Center for Biotechnology Spain
- Erasmus University Medical Center Netherlands
Nucleocytoplasmic Transport Proteins, Carcinoma, Hepatocellular, Chromosomes, Human, Pair 12, Oncogene Proteins, Fusion, Transcription, Genetic, Receptors, Retinoic Acid, Reverse Transcriptase Polymerase Chain Reaction, Chromosomes, Human, Pair 22, Liver Neoplasms, Nuclear Proteins, RNA-Binding Proteins, EMC MM-03-24-01, DNA-Binding Proteins, Histone Deacetylase Inhibitors, Retinoid X Receptors, Mutation, Humans, Enzyme Inhibitors, E1A-Associated p300 Protein, Genes, Dominant, Transcription Factors
Nucleocytoplasmic Transport Proteins, Carcinoma, Hepatocellular, Chromosomes, Human, Pair 12, Oncogene Proteins, Fusion, Transcription, Genetic, Receptors, Retinoic Acid, Reverse Transcriptase Polymerase Chain Reaction, Chromosomes, Human, Pair 22, Liver Neoplasms, Nuclear Proteins, RNA-Binding Proteins, EMC MM-03-24-01, DNA-Binding Proteins, Histone Deacetylase Inhibitors, Retinoid X Receptors, Mutation, Humans, Enzyme Inhibitors, E1A-Associated p300 Protein, Genes, Dominant, Transcription Factors
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