The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential for a subset of transcriptional and oncogenic properties of E2a-Pbx1

Leuk Lymphoma. 2009 May;50(5):816-28. doi: 10.1080/10428190902836107.

Abstract

The oncogene E2a-Pbx1 is formed by the t(1;19) translocation, which joins the N-terminal transactivation domain of E2a with the C-terminal homeodomain of PBX1. The goal of this work was to elucidate the mechanisms by which E2a-Pbx1 can lead to deregulated target gene expression. For reporter constructs it was shown that E2a-Pbx1 can activate transcription through homodimer elements (TGATTGAT) or through heterodimer elements with Hox proteins (e.g. TGATTAAT). We show a novel mechanism by which E2a-Pbx1 activates transcription of EF-9 using a promoter in intron 1 of the EF-9 gene, resulting in an aminoterminal truncated transcript. Our results indicate that the LDFS motif of E2a is essential for the transactivation of EF-9, but dispensable for transactivation of fibroblast growth factor 15. The E2a LDFS motif was also essential for proliferation of NIH3T3 fibroblasts but was dispensable for the E2a-Pbx1-induced differentiation arrest of myeloid progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins
  • Fibroblasts / cytology
  • Gene Expression Regulation, Neoplastic
  • Histone Acetyltransferases / metabolism*
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Myeloid Cells / cytology
  • NIH 3T3 Cells
  • Oncogene Proteins, Fusion / genetics*
  • Peptide Elongation Factor 2
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • Transcriptional Activation

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Oncogene Proteins, Fusion
  • Peptide Elongation Factor 2
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • TCF3 protein, human
  • pbx1 protein, human
  • E2A-Pbx1 fusion protein
  • Histone Acetyltransferases
  • KAT2A protein, human