Posttranslational modification of TEL and TEL/AML1 by SUMO-1 and cell-cycle-dependent assembly into nuclear bodies.
The E-26 transforming specific (ETS)-related gene, TEL, also known as ETV6, encodes a strong transcription repressor that is rearranged in several recurring chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. TEL is a nuclear phosphoprotein that is widely expressed in all normal tissues. TEL contains a DNA-binding domain at the ... C terminus and a helix-loop-helix domain (also called a pointed domain) at the N terminus. The pointed domain is necessary for homotypic dimerization and for interaction with the ubiquitin-conjugating enzyme UBC9. Here we show that the interaction with UBC9 leads to modification of TEL by conjugating it to SUMO-1. The SUMO-1-modified TEL localizes to cell-cycle-specific nuclear speckles that we named TEL bodies. We also show that the leukemia-associated fusion protein TEL/AML1 is modified by SUMO-1 and found in the TEL bodies, in a pattern quite different from what we observe and report for AML1. Therefore, SUMO-1 modification of TEL could be a critical signal necessary for normal functioning of the protein. In addition, the modification by SUMO-1 of TEL/AML1 could lead to abnormal localization of the fusion protein, which could have consequences that include contribution to neoplastic transformation.
Mesh Terms:
Animals, COS Cells, Cell Cycle, Cell Line, Cercopithecus aethiops, Cloning, Molecular, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Humans, Kidney, Leukemia, Erythroblastic, Acute, Mutagenesis, Site-Directed, Nuclear Proteins, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Recombinant Proteins, Repressor Proteins, SUMO-1 Protein, Saccharomyces cerevisiae, Transcription Factors, Tumor Cells, Cultured, Ubiquitins
Animals, COS Cells, Cell Cycle, Cell Line, Cercopithecus aethiops, Cloning, Molecular, Core Binding Factor Alpha 2 Subunit, DNA-Binding Proteins, Humans, Kidney, Leukemia, Erythroblastic, Acute, Mutagenesis, Site-Directed, Nuclear Proteins, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Recombinant Proteins, Repressor Proteins, SUMO-1 Protein, Saccharomyces cerevisiae, Transcription Factors, Tumor Cells, Cultured, Ubiquitins
Proc. Natl. Acad. Sci. U.S.A.
Date: Nov. 21, 2000
PubMed ID: 11078523
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