CEBPA

This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma. Activity of this protein can modulate the expression of genes involved in cell cycle regulation as well as in body weight homeostasis. Mutation of this gene is associated with acute myeloid leukemia. The use of alternative in-frame non-AUG (GUG) and AUG start codons results in protein isoforms with different lengths. Differential translation initiation is mediated by an out-of-frame, upstream open reading frame which is located between the GUG and the first AUG start codons. [provided by RefSeq, Dec 2013]

Full Name

CCAAT/Enhancer Binding Protein Alpha

Function

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. Downregulates 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).
Isoform 3:
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).
Isoform 4:
Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.

Biological Process

Brown fat cell differentiation Source: Ensembl
Cell maturation Source: Ensembl
Cellular response to lithium ion Source: Ensembl
Cellular response to organic cyclic compound Source: Ensembl
Cellular response to tumor necrosis factor Source: Ensembl
Cholesterol metabolic process Source: Ensembl
Cytokine-mediated signaling pathway Source: UniProtKB
Embryonic placenta development Source: Ensembl
Fat cell differentiation Source: UniProtKB
Generation of precursor metabolites and energy Source: ProtInc
Glucose homeostasis Source: UniProtKB
Granulocyte differentiation Source: UniProtKB
Inner ear development Source: Ensembl
Interleukin-6-mediated signaling pathway Source: ARUK-UCL
Lipid homeostasis Source: UniProtKB
Liver development Source: UniProtKB
Lung development Source: UniProtKB
Macrophage differentiation Source: Ensembl
Mitochondrion organization Source: Ensembl
Myeloid cell differentiation Source: GO_Central
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: ParkinsonsUK-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: Ensembl
Notch signaling pathway Source: Ensembl
Positive regulation of DNA-templated transcription, initiation Source: UniProtKB
Positive regulation of fat cell differentiation Source: Ensembl
Positive regulation of gene expression Source: Ensembl
Positive regulation of inflammatory response Source: ARUK-UCL
Positive regulation of macrophage activation Source: ARUK-UCL
Positive regulation of osteoblast differentiation Source: Ensembl
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of transcription by RNA polymerase III Source: UniProtKB
Regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Transcription by RNA polymerase I Source: UniProtKB
Urea cycle Source: Ensembl
viral process Source: UniProtKB-KW
white fat cell differentiation Source: Ensembl

Cellular Location

Nucleus
Isoform 4: Nucleolus

Involvement in disease

Leukemia, acute myelogenous (AML): A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.

PTM

Phosphorylation at Ser-190 is required for interaction with CDK2, CDK4 and SWI/SNF complex leading to cell cycle inhibition. Dephosphorylated at Ser-190 by protein phosphatase 2A (PP2A) through PI3K/AKT signaling pathway regulation (PubMed:15107404). Phosphorylation at Thr-226 and Thr-230 by GSK3 is constitutive in adipose tissue and lung. In liver, both Thr-226 and Thr-230 are phosphorylated only during feeding but not during fasting. Phosphorylation of the GSK3 consensus sites selectively decreases transactivation activity on IRE-controlled promoters.
Sumoylated, sumoylation blocks the inhibitory effect on cell proliferation by disrupting the interaction with SMARCA2.
Ubiquitinated by COP1 upon interaction with TRIB1.