Abstract:
:The MTG (Myeloid Translocation Gene) proteins are a family of novel transcriptional corepressors. We report that MTG16a, a protein isoform encoded by the MTG16 gene deranged by the t (16; 21) in myeloid malignancies, is targeted to the nucleolus. The amino acid sequence necessary for nucleolar localization was mapped to the MTG16a N-terminal region. MTG16a, like MTG8, the nuclear corepressor deranged by the t (8; 21), is capable to interact with specific histone deacetylases (HDACs) suggesting that the protein may mediate silencing of nucleolar gene transcription. In addition, MTG16a is capable to form oligomers with other MTG proteins. As a consequence of the t (16; 21) the AML1 DNA-binding domain replaces the MTG16a N-terminal region. The AML1-MTG16 fusion protein is targeted to the nucleoplasm where it is capable to oligomerize with MTG16a and interact with HDAC1 and HDAC3. The deficiency of HDAC-containing complexes at nucleolar sites and the accumulation of HDAC-containing complexes at AML1-sites may be critical in the pathogenesis of t (16; 21) myeloid malignancies.
journal_name
Oncogenejournal_title
Oncogeneauthors
Hoogeveen AT,Rossetti S,Stoyanova V,Schonkeren J,Fenaroli A,Schiaffonati L,van Unen L,Sacchi Ndoi
10.1038/sj.onc.1205882subject
Has Abstractpub_date
2002-09-26 00:00:00pages
6703-12issue
43eissn
0950-9232issn
1476-5594journal_volume
21pub_type
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