Michael Waterman
Faculty Member
Last active: 2/12/2015

Protein kinase A-dependent transactivation by the E2A-Pbx1 fusion protein.

Ogo A, Waterman MR, Kamps MP, Kagawa N
J Biol Chem. 1995 270 (43): 25340-3

PMID: 7592695 · DOI:10.1074/jbc.270.43.25340

The chimeric gene E2A-PBX1 is formed by the t(1;19) chromosomal translocation exclusively associated with pediatric pre-B cell acute lymphoblastic leukemia (pre-B ALL). The resultant fusion protein from this chimeric gene contains the DNA-binding homeodomain of Pbx1. The first and only functional Pbx1 binding site has been localized in bovine CYP17 to a sequence (CRS1) that participates in cAMP-dependent transcription 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, transcription of genes not normally expressed in these cells leading to arrest of differentiation at the pre-B cell stage. We have now shown that reporter genes comprising CRS1 are activated transcriptionally by protein kinase A (PKA) in the pre-B cell line 697, which endogenously expresses the fusion protein, and that overexpression of E2A-Pbx1 in additional cell lines enhances transcription of reporter genes in a PKA-dependent fashion. Thus, it seems plausible that arrest in the pre-B stage leading to pre-B ALL includes cAMP-dependent activation of E2A-Pbx1.

MeSH Terms (16)

Animals Base Sequence Cattle Colforsin Cyclic AMP Cyclic AMP-Dependent Protein Kinases Genes, Reporter Homeodomain Proteins Molecular Sequence Data Nuclear Proteins Oncogene Proteins, Fusion Protein Binding Recombinant Proteins Steroid 17-alpha-Hydroxylase Transcription, Genetic Transcriptional Activation

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