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Translational regulation of c/ebp alpha and c/ebp beta transcription factors. Implications for myeloid development and leukemic transformation


C/EBPa and B mediate tissue-specific gene expression, cellular differentiation and growth arrest. C/EBPB plays a central role in the differentiation of myelomonocytic cells and in their leukemic transformation. C/EBP function in transcription regulation is dependent on the relative level of two antagonising isoforms, a transactivating and a repressing isoform, both for C/EBPa and B.
The synthesis of N-terminally truncated isoforms from internal start codons depends on an, evolutionary highly conserved, small upstream open reading frame (uORF) mediating delayed translation reinitiation. We hypothesise that this special mRNA structure senses translation initiation factor activity providing the mechanism for C/EBP isoform ratio modulation.
We propose a detailed analysis of the relationship between C/EBPa and B mRNA structure and translation initiation factor activity especially of eIF-2 which is known to be a key factor for translation reinitiation. One of the mechanisms which might play a part in transformation is deregulation of translational control generating unbalanced C/EBP isoform ra

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Stiftung Max-Delbrück-Centrum für Molekulare Medizin
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13122 Berlin

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