8k8c

Crystal structure of C/EBPalpha BZIP domain bound to a high affinity DNA

spinqualitylabelsall models 8k8c, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8k8c is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.06Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CEBPA_HUMAN Acute myeloid leukemia with CEBPA somatic mutations;Acute myeloid leukemia with t(8;21)(q22;q22) translocation;Inherited acute myeloid leukemia. The disease is caused by variants affecting the gene represented in this entry. Function CEBPA_HUMAN Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes (PubMed:11242107). During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (By similarity). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Down-regulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters. Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity).[UniProtKB:P05554][UniProtKB:P53566] Can act as dominant-negative. Binds DNA and have transctivation activity, even if much less efficiently than isoform 2. Does not inhibit cell proliferation (PubMed:14660596).[UniProtKB:P05554][UniProtKB:P53566] Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.

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