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 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.

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