The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential for a subset of transcriptional and oncogenic properties of E2a-Pbx1.
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.
Scheele
Jürgen S
JS
Department of Medicine I and Pharmacology I, University Hospital Freiburg, Freiburg, Germany. juergen.scheele@uniklinik-freiburg.de
Kolanczyk
Mateusz
M
Gantert
Melanie
M
Zemojtel
Tomasz
T
Dorn
Annette
A
Sykes
David B
DB
Sykes
David P
DP
Möbest
Dietrich C C
DC
Kamps
Mark P
MP
Räpple
Daniel
D
Duchniewicz
Marlena
M
D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000502:physiology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000166:cytology; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000166:cytology; D041681:NIH 3T3 Cells; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020652:Peptide Elongation Factor 2; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D015533:Transcriptional Activation; D000099224:p300-CBP-Associated Factor
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D020652:Peptide Elongation Factor 2; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C407909:TCF3 protein, human; C083400:PBX1 protein, human; C089847:E2A-Pbx1 fusion protein; C501179:KAT2A protein, human; D000099224:p300-CBP-Associated Factor