E4BP4 expression is regulated by the t(17;19)-associated oncoprotein E2A-HLF in pro-B cells.
The E4BP4 basic leucine zipper (bZIP) transcription factor is regulated by interleukin-3 (IL-3) in pro-B cells and has been reported to promote survival of the murine IL-3-dependent pro-B cell lines, FL5.12 and Baf-3. The E2A-HLF oncoprotein arises from a t(17;19) translocation in childhood pro-B cell acute lymphoblastic leukaemia and acts as an anti-apoptotic factor in FL5.12 and Baf-3 cells. To assess the functions of E2A-HLF and E4BP4 in cell survival, a tetracycline-inducible system was established in Baf-3 cells to express E4BP4 or E2A-HLF. Upon IL-3 withdrawal, expression of E2A-HLF conferred resistance to apoptosis whereas overexpression of E4BP4 did not. E4BP4 and E2A-HLF both recognized the same DNA sequence in reporter gene assays, but had opposite effects on transcription. E2A-HLF acts as a transcriptional activator and E4BP4 as a transcriptional repressor. Furthermore, E4BP4 is a downstream transcriptional target of E2A-HLF. Our data suggests that the overexpression of E4BP4 is unable to block apoptosis induced by IL-3 withdrawal and that the expression of E2A-HLF does not replace the function of E4BP4 in mediating survival.
Yeung
Jenny
J
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London, UK.
O'Sullivan
Elaine
E
Hubank
Mike
M
Brady
Hugh J M
HJ
D017209:Apoptosis / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D051790:G-Box Binding Factors; D015870:Gene Expression; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C076554:E2a-Hlf fusion protein, human; D051790:G-Box Binding Factors; D007377:Interleukin-3; C497440:NFIL3 protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D004318:Doxycycline