FORMATION OF IN-VIVO COMPLEXES BETWEEN THE TAL1 AND E2A POLYPEPTIDES OF LEUKEMIC T-CELLS

Tumor-specific activation of the TAL1 gene occurs in almost-equal-to 2 5% of patients with T-cell acute lymphoblastic leukemia (T-ALL). The T AL1 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-hybri d procedure and co-immunoprecipitation analysis, to demonstrate that T AL1 and E2A polypeptides also associate in vivo. These studies show th at 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 d oes not self-associate to form homodimeric complexes, implying that th e in vivo functions of TAL1 depend on heterologous interaction with ot her bHLH proteins such as E12 and E47. Co-immunoprecipitation analysis revealed the presence of endogenous TAL1/E2A complexes in Jurkat cell s, a leukemic line derived from a T-ALL patient. Thus, the malignant p roperties of TAL1 may be due to obligate interaction with the E2A poly peptides.