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.
Chakrabarti
S R
SR
Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA.
Sood
R
R
Nandi
S
S
Nucifora
G
G
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D004915:Leukemia, Erythroblastic, Acute; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D012441:Saccharomyces cerevisiae; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism*; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; D014452:Ubiquitins; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human