Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression

TEL is a transcriptional repressor that is a frequent target of chromosomal translocations in a large number of hematalogical malignancies. These rearrangements fuse a potent oligomerization module, the SAM domain of TEL, to a variety of tyrosine kinases or transcriptional regulatory proteins. The s...

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Bibliographic Details
Published in:The EMBO journal 2001-08, Vol.20 (15), p.4173-4182
Main Authors: Kim, Chongwoo A., Phillips, Martin L., Kim, Woojae, Gingery, Mari, Tran, Hoang H., Robinson, Michael A., Faham, Salem, Bowie, James U.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
chromatin silencing
Crystallography, X-Ray
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
ETS Translocation Variant 6 Protein
Humans
leukemia
Leukemia, Myelomonocytic, Chronic
Molecular Sequence Data
oncogene
Pointed domain
polycomb group proteins
Polymers - chemistry
Protein Structure, Secondary
Protein Structure, Tertiary
Proto-Oncogene Proteins c-ets
Recombinant Fusion Proteins - biosynthesis
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - physiology
Repressor Proteins - biosynthesis
Repressor Proteins - chemistry
Repressor Proteins - genetics
Repressor Proteins - physiology
Solubility
TEL protein
Transcription, Genetic
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Description
Summary:TEL is a transcriptional repressor that is a frequent target of chromosomal translocations in a large number of hematalogical malignancies. These rearrangements fuse a potent oligomerization module, the SAM domain of TEL, to a variety of tyrosine kinases or transcriptional regulatory proteins. The self‐associating property of TEL–SAM is essential for cell transformation in many, if not all of these diseases. Here we show that the TEL–SAM domain forms a helical, head‐to‐tail polymeric structure held together by strong intermolecular contacts, providing the first clear demonstration that SAM domains can polymerize. Our results also suggest a mechanism by which SAM domains could mediate the spreading of transcriptional repression complexes along the chromosome.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/20.15.4173