C/EBPalpha induces PU.1 and interacts with AP-1 and NF-kappaB to regulate myeloid development.
C/EBPalpha and PU.1 are key regulators of early myeloid development. Mice lacking C/EBPalpha or PU.1 have reduced granulocytes and monocytes. Consistent with a model in which induction of PU.1 by C/EBPalpha contributes to monocyte lineage specification, mice with reduced PU.1 have diminished monocytes but retain granulocytes, C/EBPalpha directly activates PU.1 gene transcription, and exogenous C/EBPalpha increases monocytic lineage commitment from bipotential myeloid progenitors. In addition to C/EBPalpha, AP-1 proteins also have the capacity to induce monocytic maturation. C/EBPalpha:c-Jun or C/EBPalpha:c-Fos leucine zipper heterodimers induce monopoiesis more potently than C/EBPalpha or c-Jun homodimers or c-Fos:c-Jun heterodimers. C/EBPs and NF-kappaB cooperatively regulate numerous genes during the inflammatory response. The C/EBPalpha basic region interacts with NF-kappaB p50, but not p65, to induce bcl-2, and this interaction may be relevant to myeloid cell survival and development.
Division of Pediatric Oncology, Johns Hopkins University, CRB I, Room 253, 1650 Orleans St., Baltimore, MD 21231, USA. afriedm2@jhmi.edu
Alan D
AD
Friedman
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D022423:Myeloid Cells / Q000378:metabolism*; D038042:Myelopoiesis; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D022763:CCAAT-Enhancer-Binding Protein-alpha; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D000099232:Proto-Oncogene Protein Spi-1