Transformation properties of the E2a-Pbx1 chimeric oncoprotein: fusion with E2a is essential, but the Pbx1 homeodomain is dispensable.

摘要: The t(1;19) chromosomal translocation in acute lymphoblastic leukemias creates chimeric E2a-Pbx1 oncoproteins that can act as DNA-binding activators of transcription. A structural analysis the functional domains showed portions both E2a and Pbx1 were essential for transformation NIH 3T3 cells transcriptional activation synthetic reporter genes containing PBX1 consensus binding sites. Hyperexpression wild-type or experimentally truncated proteins was insufficient transformation, consistent with their inability to activate When fused E2a, Pbx-related Pbx2 Pbx3 also competent, demonstrating all known members this highly similar subfamily homeodomain have latent oncogenic potential. contributions chimeras localized transactivation motifs AD1 AD2, mutation significantly impaired transformation. Either amino acids flanking region could mediate when E2a. However, not since a mutant protein (E2a-Pbx delta HD) lacking efficiently transformed fibroblasts induced malignant lymphomas transgenic mice. Thus, mediated by oncoprotein is absolutely dependent on acquired from but optional. latter finding suggests may interact cellular assist alterations gene expression responsible oncogenesis even absence homeodomain-DNA interactions.