title: Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, DOE Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, CA, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Kim
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.forename: W
authors.initials: W
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Gingery
authors.forename: H H
authors.initials: HH
authors.lastname: Tran
authors.forename: M A
authors.initials: MA
authors.lastname: Robinson
authors.forename: S
authors.initials: S
authors.lastname: Faham
authors.forename: J U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic; D008969:Molecular Sequence Data; D011108:Polymers / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D012995:Solubility; D014158:Transcription, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D011108:Polymers; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein