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Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression
Author(s) -
Kim Chongwoo A.,
Phillips Martin L.,
Kim Woojae,
Gingery Mari,
Tran Hoang H.,
Robinson Michael A.,
Faham Salem,
Bowie James U.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.15.4173
Subject(s) - biology , psychological repression , repressor , chromosomal translocation , transcriptional regulation , microbiology and biotechnology , kinase , protein kinase domain , genetics , transcription factor , gene , gene expression , mutant
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.