Cebpa

CCAAT/enhancer-binding protein alpha is a transcription factor involved in the differentiation of certain blood cells. For details on the CCAAT structural motif in gene enhancers and on CCAAT/Enhancer Binding Proteins see the specific page.

CEBPA
Identifiers
Aliases	CEBPA, C/EBP-alpha, CEBP, CCAAT/enhancer binding protein alpha, CCAAT enhancer binding protein alpha
External IDs	OMIM: 116897 MGI: 99480 HomoloGene: 3211 GeneCards: CEBPA
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.11 Start 33,299,934 bp End 33,302,534 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 B2|7 21.02 cM Start 34,818,718 bp End 34,821,353 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nipple human penis skin of abdomen right lobe of liver monocyte adipose tissue subcutaneous adipose tissue vulva abdominal fat synovial joint Top expressed in brown adipose tissue subcutaneous adipose tissue white adipose tissue lip right lung gallbladder skin of back left lobe of liver right lung lobe skin of abdomen More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding sequence-specific DNA binding protein homodimerization activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity transcription coactivator activity transcription factor binding RNA polymerase II cis-regulatory region sequence-specific DNA binding kinase binding protein binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component transcription regulator complex RNA polymerase II transcription regulator complex nucleolus nucleus nucleoplasm intracellular membrane-bounded organelle Biological process Notch signaling pathway transcription by RNA polymerase I myeloid cell differentiation regulation of transcription, DNA-templated cellular response to lithium ion glucose homeostasis negative regulation of cyclin-dependent protein serine/threonine kinase activity lung development cytokine-mediated signaling pathway urea cycle regulation of transcription by RNA polymerase II cellular response to organic cyclic compound mitochondrion organization embryonic placenta development cholesterol metabolic process negative regulation of cell cycle negative regulation of transcription by RNA polymerase II cell maturation generation of precursor metabolites and energy transcription, DNA-templated macrophage differentiation multicellular organism development positive regulation of transcription, DNA-templated positive regulation of osteoblast differentiation granulocyte differentiation regulation of cell population proliferation brown fat cell differentiation lipid homeostasis white fat cell differentiation inner ear development liver development viral process negative regulation of transcription, DNA-templated positive regulation of fat cell differentiation positive regulation of transcription by RNA polymerase III fat cell differentiation positive regulation of proteasomal ubiquitin-dependent protein catabolic process positive regulation of transcription by RNA polymerase II negative regulation of cell population proliferation transcription by RNA polymerase II cellular response to tumor necrosis factor positive regulation of DNA-templated transcription, initiation positive regulation of macrophage activation positive regulation of inflammatory response interleukin-6-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1050 12606 Ensembl ENSG00000245848 ENSMUSG00000034957 UniProt P49715 P53566 RefSeq (mRNA) NM_004364 NM_001285829 NM_001287424 NM_001287435 NM_001287514 NM_001287515 NM_001287521 NM_001287523 NM_007678 RefSeq (protein) NP_001272758 NP_001274353 NP_001274364 NP_004355 NP_001274443 NP_001274444 NP_001274450 NP_001274452 NP_031704 Location (UCSC) Chr 19: 33.3 – 33.3 Mb Chr 7: 34.82 – 34.82 Mb PubMed search
Wikidata
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The protein encoded by this intronless gene is a bZIP transcription factor which can bind as a homodimer to certain promoters and gene enhancers. It can also form heterodimers with the related proteins CEBP-beta and CEBP-gamma, as well as distinct transcription factors such as c-Jun. The encoded protein is a key regulator of adipogenesis (the process of forming new fat cells) and the accumulation of lipids in those cells, as well as in the metabolism of glucose and lipids in the liver. The protein has been shown to bind to the promoter and modulate the expression of the gene encoding leptin, a protein that plays an important role in body weight homeostasis. Also, the encoded protein can interact with CDK2 and CDK4, thereby inhibiting these kinases and causing cultured cells to stop dividing. In addition, CEBPA is essential for myeloid lineage commitment and therefore required both for normal mature granulocyte formation and for the development of abnormal acute myeloid leukemia.

There are two major categories which CEBPA mutations can be categorized into. One category of mutations prevent CCAAT/enhancer-binding protein alpha DNA binding by altering its COOH-terminal basic leucine zipper domain. The other category of mutations disrupt the translation of the CCAAT/enhancer-binding protein alpha NH₂ terminus. CEBPA mutations, which result in diminished CCAAT/enhancer-binding protein alpha activity, contribute to the transformation of myeloid antecedents.

CEBPA has been shown to interact with Cyclin-dependent kinase 2 and Cyclin-dependent kinase 4.

It has been shown that mutation of CEBPA has been linked to good outcome in both adult and pediatric acute myeloid leukemia patients.

Significance in acute myeloid leukemia

Acute myeloid leukemia is characterized by genetic abnormalities in hematopoietic progenitors. This includes excessive proliferation of blasts, and blocking the hematopoiesis of granulocytes. It has been shown that suppression of CEBPA expression and blocking of CCAAT/enhancer-binding protein alpha stops the differentiation of myeloid progenitors. For this reason, CCAAT/enhancer-binding protein alpha's role during granulocyte differentiation and CEBPA's role as a tumor suppressor gene is critically important in the prognosis of acute myeloid leukemia.

Prognostic significance of CEBPA mutations

CCAAT/enhancer-binding protein alpha, the transcription factor that is encoded by CEBPA, is very important in the differentiation of immature granulocytes. Mutation of the CEBPA gene has been shown to play a crucial role in leukemogenesis and prognosis in acute myeloid leukemia patients. In recent studies CEBPA mutations were found in between 7% and 15% of patients with acute myeloid leukemia. The three different types of mutations seen in these AML patients include germ-line N-terminal mutation, N-terminal frameshift mutation, and C-terminal mutation. These mutations are most frequently found in acute myeloid leukemia M1 or acute myeloid leukemia M2. Many reports link CEBPA mutations with a favorable outcome in acute myeloid leukemia. This is because these mutations are likely to induce differentiation arrest in these patients. Patients with CEBPA mutations have longer remission duration and survival time than those without the mutations. Therefore, the presence of CEBPA mutations are directly associated with a more favorable course for the progression of the disease.

Significance in solid tumors

Recently it has been shown that epigenetic modification of the distal promoter region of CEBPA has resulted in downregulation of CEBPA expression in pancreatic cancer cells, lung cancer, and head and neck squamous cell carcinoma.

Methylation of CEBPA as a prognostic biomarker in AML patients

A recent study has found that higher levels of CEBPA methylation are directly proportionate with treatment response. The complete response rate increased proportionately with the level of CEBPA methylation. For this reason it has been proposed that methylation of CEBPA could be a very useful biomarker in acute myeloid leukemia prognosis.

• Ccaat-enhancer-binding proteins