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.
Kim
C A
CA
Department of Chemistry and Biochemistry, DOE Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, CA, USA.
Phillips
M L
ML
Kim
W
W
Gingery
M
M
Tran
H H
HH
Robinson
M A
MA
Faham
S
S
Bowie
J U
JU
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
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