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.
Friedman
Alan D
AD
Division of Pediatric Oncology, Johns Hopkins University, CRB I, Room 253, 1650 Orleans St., Baltimore, MD 21231, USA. afriedm2@jhmi.edu
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