Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic T cells.
Tumor-specific activation of the TAL1 gene occurs in approximately 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL). The TAL1 gene products possess a basic helix-loop-helix (bHLH) domain that interacts in vitro with the bHLH proteins (E12 and E47) encoded by the E2A locus. We have now applied two independent methods, the two-hybrid procedure and co-immunoprecipitation analysis, to demonstrate that TAL1 and E2A polypeptides also associate in vivo. These studies show that the bHLH domain of TAL1 selectively interacts with the bHLH domains of E12 and E47, but not with the Id1 helix-loop-helix protein. TAL1 does not self-associate to form homodimeric complexes, implying that the in vivo functions of TAL1 depend on heterologous interaction with other bHLH proteins such as E12 and E47. Co-immunoprecipitation analysis revealed the presence of endogenous TAL1/E2A complexes in Jurkat cells, a leukemic line derived from a T-ALL patient. Thus, the malignant properties of TAL1 may be due to obligate interaction with the E2A polypeptides.
Hsu
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HL
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Wadman
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Baer
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D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C544912:TCF7L1 protein, human; C067143:TAL1 protein, human