A. Ogo et al., PROTEIN-KINASE A-DEPENDENT TRANSACTIVATION BY THE E2A-PBX1 FUSION PROTEIN, The Journal of biological chemistry, 270(43), 1995, pp. 25340-25343
The chimeric gene E2A-PBX1 is formed by the t(1;19) chromosomal transl
ocation exclusively associated with pediatric pre-B cell acute lymphob
lastic leukemia (pre-B ALL). The resultant fusion protein from this ch
imeric gene contains the DNA-binding homeodomain of Pbx1. The first an
d only functional Pbx1 binding site has been localized in bovine CYP17
to a sequence (CRS1) that participates in cAMP-dependent transcriptio
n of this gene encoding the steroid hydroxylase, 17 alpha-hydroxylase
cytochrome P450. Because Pbx1 is not expressed in pre-B cells, it may
be possible that the E2a-Pbx1 fusion protein expressed in pre-B cells
having this translocation will activate, in response to cAMP, transcri
ption of genes not normally expressed in these cells leading to arrest
of differentiation at the pre-B cell stage. We have now shown that re
porter genes comprising CRS1 are activated transcriptionally by protei
n kinase A (PKA) in the pre-B cell line 697, which endogenously expres
ses the fusion protein, and that overexpression of E2A-Pbx1 in additio
nal cell lines enhances transcription of reporter genes in a PKA-depen
dent fashion. Thus, it seems plausible that arrest in the pre-B stage
leading to pre-B ALL includes cAMP-dependent activation of E2A-Pbx1.