Genomes and Genes
Gene Symbol: Cebpa
Description: CCAAT/enhancer binding protein alpha
Alias: DBPCEP, CCAAT/enhancer-binding protein alpha, C/EBP alpha, CAAT/enhancer-binding protein, DNA-binding protein, CCAAT/enhancer binding protein (C/EBP), alpha
- Courselaud B, Pigeon C, Inoue Y, Inoue J, Gonzalez F, Leroyer P, et al. C/EBPalpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism. J Biol Chem. 2002;277:41163-70 pubmed..Taken together, these data demonstrate that C/EBPalpha is likely to be a key regulator of HEPC gene transcription and provide a novel mechanism for cross-talk between the C/EBP pathway and iron metabolism. ..
- Wang G, Iakova P, Wilde M, Awad S, Timchenko N. Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity. Genes Dev. 2004;18:912-25 pubmed..These data provide a molecular basis for the development of liver tumors in which the activation of PI3K/Akt pathway neutralizes C/EBPalpha growth inhibitory activity. ..
- Ramji D, Foka P. CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem J. 2002;365:561-75 pubmed..This review deals with the structure, biological function and the regulation of the C/EBP family. ..
- Porse B, Pedersen TA -, Xu X, Lindberg B, Wewer U, Friis Hansen L, et al. E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo. Cell. 2001;107:247-58 pubmed
- Ross S, Hemati N, Longo K, Bennett C, Lucas P, Erickson R, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950-3 pubmed..Disruption of Wnt signaling also causes transdifferentiation of myoblasts into adipocytes in vitro, highlighting the importance of this pathway not only in adipocyte differentiation but also in mesodermal cell fate determination. ..
- Muller C, Calkhoven C, Sha X, Leutz A. The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF complex for proliferation arrest. J Biol Chem. 2004;279:7353-8 pubmed
- Enwright J, Kawecki Crook M, Voss T, Schaufele F, Day R. A PIT-1 homeodomain mutant blocks the intranuclear recruitment of the CCAAT/enhancer binding protein alpha required for prolactin gene transcription. Mol Endocrinol. 2003;17:209-22 pubmed..Together our results suggest that the intranuclear positioning of these factors determines whether they activate or silence PRL promoter activity. ..
- Calkhoven C, Muller C, Leutz A. Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes Dev. 2000;14:1920-32 pubmed..Our results demonstrate that the translational controlled ratio of C/EBPalpha and C/EBPbeta isoform expression determines cell fate. ..
- Pabst T, Mueller B, Zhang P, Radomska H, Narravula S, Schnittger S, et al. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet. 2001;27:263-70 pubmedThe transcription factor C/EBPalpha (for CCAAT/enhancer binding protein-alpha; encoded by the gene CEBPA) is crucial for the differentiation of granulocytes...
- Blalock E, Geddes J, Chen K, Porter N, Markesbery W, Landfield P. Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci U S A. 2004;101:2173-8 pubmed..These findings suggest a new model of AD pathogenesis in which a genomically orchestrated up-regulation of tumor suppressor-mediated differentiation and involution processes induces the spread of pathology along myelinated axons. ..
- Ossipow V, Descombes P, Schibler U. CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials. Proc Natl Acad Sci U S A. 1993;90:8219-23 pubmed..The production of multiple proteins from a single mRNA is not only shared between different C/EBP family members but also appears to be conserved in vertebrate evolution. ..
- Landschulz W, Johnson P, Adashi E, Graves B, McKnight S. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988;2:786-800 pubmed..A 60-amino-acid segment located within the DNA-binding domain of C/EBP bears sequence similarity to the products of the myc and fos oncogenes. ..
- Sandhir R, Berman N. Age-dependent response of CCAAT/enhancer binding proteins following traumatic brain injury in mice. Neurochem Int. 2010;56:188-93 pubmed publisher..In addition elevated C/EBPdelta levels following TBI in the aged brain may play a role in the link between TBI and Alzheimer's disease. ..
- Juan T, Veniant M, Helmering J, Babij P, Baker D, Damore M, et al. Identification of three loci affecting HDL-cholesterol levels in a screen for chemically induced recessive mutations in mice. J Lipid Res. 2009;50:534-45 pubmed publisher..These results illustrate the use of a hybrid background for simultaneous screening and mapping of mutagenized pedigrees of mice and identification of three novel alleles of HDL-cholesterol phenotypes...
- Kennell J, O Leary E, Gummow B, Hammer G, MacDougald O. T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol Cell Biol. 2003;23:5366-75 pubmed..Thus, we propose that TCF-4N inhibits coactivation by beta-catenin of TCF/LEF transcription factors and potentiates the coactivation by beta-catenin of other transcription factors, such as SF-1 and C/EBPalpha. ..
- Heath V, Suh H, Holman M, Renn K, Gooya J, Parkin S, et al. C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood. 2004;104:1639-47 pubmed..These findings show that C/EBPalpha deficiency results in hyperproliferation of HPCs and a block in the ability of multipotential progenitors to differentiate into bipotential granulocyte/macrophage progenitors and their progeny. ..
- Zhong J, Lardinois D, Szilard J, Tamm M, Roth M. Rat mesothelioma cell proliferation requires p38? mitogen activated protein kinase and C/EBP-?. Lung Cancer. 2011;73:166-70 pubmed publisher..From this rat model, we conclude that in pleural mesothelioma, p38? in C/EBP-? mediate proliferation and thus may represent new targets in mesothelioma therapy. ..
- Bennett C, Ross S, Longo K, Bajnok L, Hemati N, Johnson K, et al. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002;277:30998-1004 pubmed..Finally, we demonstrate that disruption of extracellular Wnt signaling by expression of secreted Frizzled related proteins causes spontaneous adipocyte conversion. ..
- Stephens J, Pekala P. Transcriptional repression of the C/EBP-alpha and GLUT4 genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. Regulations is coordinate and independent of protein synthesis. J Biol Chem. 1992;267:13580-4 pubmed..In addition to the transcriptional effect, we report that TNF-induced destabilization of these mRNAs contributes to decreased expression of all three genes. ..
- Dinić S, Bogojevic D, Petrović M, Poznanovic G, Ivanovic Matic S, Mihailovic M. C/EBP alpha and C/EBP beta regulate haptoglobin gene expression during rat liver development and the acute-phase response. Mol Biol Rep. 2005;32:141-7 pubmed..These results indicate that Hp gene transcription is regulated by C/EBP alpha during normal liver development, whereas C/EBP beta is involved in the AP regulation during the later phase of differentiation and in the adult. ..
- Zhang P, Iwasaki Arai J, Iwasaki H, Fenyus M, Dayaram T, Owens B, et al. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha. Immunity. 2004;21:853-63 pubmed..Therefore, C/EBP alpha is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity. ..
- Qi X, Nishida J, Chaves L, Ohmori K, Huang H. CCAAT/enhancer-binding protein alpha (C/EBPalpha) is critical for interleukin-4 expression in response to FcepsilonRI receptor cross-linking. J Biol Chem. 2011;286:16063-73 pubmed publisher..Our study demonstrates that C/EBP?, in cooperation with NFAT, directly regulates Il4 gene transcription. ..
- Rodriguez Antona C, Bort R, Jover R, Tindberg N, Ingelman Sundberg M, Gomez Lechon M, et al. Transcriptional regulation of human CYP3A4 basal expression by CCAAT enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma. Mol Pharmacol. 2003;63:1180-9 pubmed..These findings revealed that C/EBP alpha and HNF-3 gamma cooperatively regulate CYP3A4 expression in hepatic cells by a mechanism that probably involves chromatin remodeling. ..
- Fei Z, Bera T, Liu X, Xiang L, Pastan I. Ankrd26 gene disruption enhances adipogenesis of mouse embryonic fibroblasts. J Biol Chem. 2011;286:27761-8 pubmed publisher..We conclude that Ankrd26 gene disruption promotes adipocyte differentiation at both the progenitor commitment and differentiation steps and that ERK activation plays a role in this process. ..
- Begay V, Smink J, Leutz A. Essential requirement of CCAAT/enhancer binding proteins in embryogenesis. Mol Cell Biol. 2004;24:9744-51 pubmed..Our data thus reveal novel essential, redundant, and dosage dependent functions of C/EBPs. ..
- Shiojiri N, Takeshita K, Yamasaki H, Iwata T. Suppression of C/EBP alpha expression in biliary cell differentiation from hepatoblasts during mouse liver development. J Hepatol. 2004;41:790-8 pubmed..These data suggest that the suppression of C/EBP alpha expression may be prerequisite to biliary cell differentiation in the hepatoblast population and one of its earliest signs. ..
- Samuelsson L, Stromberg K, Vikman K, Bjursell G, Enerback S. The CCAAT/enhancer binding protein and its role in adipocyte differentiation: evidence for direct involvement in terminal adipocyte development. EMBO J. 1991;10:3787-93 pubmed..These findings strongly support the view that C/EBP is a necessary component of terminal adipocyte differentiation. ..
- Shin S, Kim K, Kim J, Yoon S, Choi I, Yang Y. Dexamethasone reverses TGF-beta-mediated inhibition of primary rat preadipocyte differentiation. FEBS Lett. 2003;543:25-30 pubmed..These results indicate that dexamethasone reverses the TGF-beta-mediated suppression of adipocyte differentiation by regulating the expression of C/EBPalpha and PPARgamma, which is dependent on the cellular context. ..
- Miller M, Shuman J, Sebastian T, Dauter Z, Johnson P. Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha. J Biol Chem. 2003;278:15178-84 pubmed..Our studies also help to explain the phenotypes of mice carrying targeted mutations in the C/EBPalpha bZIP region. ..
- Shiroyama N, Miyake Y. [Analysis of focal macular ERG in idiopathic central serous chorioretinopathy]. Nippon Ganka Gakkai Zasshi. 1990;94:1048-56 pubmed..The present study showed that the abnormal pattern of MERG in CSC cannot be explained simply by the assumption of receptor disorientation or a disturbance of photopigment regeneration by analyzing similar conditions in normal eyes. ..
- Numata A, Shimoda K, Kamezaki K, Haro T, Kakumitsu H, Shide K, et al. Signal transducers and activators of transcription 3 augments the transcriptional activity of CCAAT/enhancer-binding protein alpha in granulocyte colony-stimulating factor signaling pathway. J Biol Chem. 2005;280:12621-9 pubmed..Additionally, cooperation of C/EBPalpha with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor. ..
- Rosenberg E, Li F, Reisher S, Wang M, Gonzales L, Ewing J, et al. Members of the C/EBP transcription factor family stimulate expression of the human and rat surfactant protein A (SP-A) genes. Biochim Biophys Acta. 2002;1575:82-90 pubmed..The data indicate that C/EBPs facilitate SP-A gene expression, possibly by overcoming transcriptional silencing. ..
- Fazio S, Linton M, Hasty A, Swift L. Recycling of apolipoprotein E in mouse liver. J Biol Chem. 1999;274:8247-53 pubmed..These studies show that apoE recycling is a physiologic phenomenon in vivo and establish the presence of a unique pathway of intracellular processing of apoE-containing remnant lipoproteins. ..
- Ubeda M, Wang X, Zinszner H, Wu I, Habener J, Ron D. Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element. Mol Cell Biol. 1996;16:1479-89 pubmed..We conclude that CHOP may serve a dual role both as an inhibitor of the ability of C/EBP proteins to activate some target genes and as a direct activator of others. ..
- Pedersen T, Bereshchenko O, Garcia Silva S, Ermakova O, Kurz E, Mandrup S, et al. Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene expression in vivo. EMBO J. 2007;26:1081-93 pubmed
- Tong Q, Tsai J, Tan G, Dalgin G, Hotamisligil G. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Mol Cell Biol. 2005;25:706-15 pubmed
- Wang K, Brems J, Gamelli R, Holterman A. C/EBP? and C/EBP? binding proteins modulate hepatocyte apoptosis through iNOS signaling pathway. Biochim Biophys Acta. 2011;1813:1395-403 pubmed publisher..These findings indicate that C/EBP? and C/EBP? regulate the iNOS expression, which may further modify cell responses such as apoptosis and cell survival. ..
- Shimizu H, Yamamoto K. NF-kappa B and C/EBP transcription factor families synergistically function in mouse serum amyloid A gene expression induced by inflammatory cytokines. Gene. 1994;149:305-10 pubmed
- Chen W, Zhu G, Hao L, Wu M, Ci H, Li Y. C/EBP? regulates osteoclast lineage commitment. Proc Natl Acad Sci U S A. 2013;110:7294-9 pubmed publisher..These discoveries establish C/EBP? as the key transcriptional regulator of OC lineage commitment, providing a unique therapeutic target for diseases of excessive bone resorption, such as osteoporosis and arthritis. ..
- Xu Y, Wu C, Wu Y, Tong P, Jin H, Yu N, et al. Epimedium-derived flavonoids modulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats via Wnt/?-catenin signal pathway activation. Chin J Integr Med. 2012;18:909-17 pubmed publisher
- Wang X, Huang G, Mei S, Qian J, Ji J, Zhang J. Over-expression of C/EBP-alpha induces apoptosis in cultured rat hepatic stellate cells depending on p53 and peroxisome proliferator-activated receptor-gamma. Biochem Biophys Res Commun. 2009;380:286-91 pubmed publisher..In addition, Fas, FasL, DR4, DR5, and TRAIL were studied. The results indicated that the death receptor pathway was mainly involved and regulated by PPAR-gamma and p53 in the process of apoptosis triggered by C/EBP-alpha in HSCs. ..
- Sato Y, Miyake K, Kaneoka H, Iijima S. Sumoylation of CCAAT/enhancer-binding protein alpha and its functional roles in hepatocyte differentiation. J Biol Chem. 2006;281:21629-39 pubmed..This result suggests that BRG1 down-regulates the expression of the dihydrofolate reductase gene. These findings provide the insight that SUMO acts as a space regulator, which affects protein-protein interactions. ..
- Liu H, Perrier S, Lipina C, Finlay D, McLauchlan H, Hastie C, et al. Functional characterisation of the regulation of CAAT enhancer binding protein alpha by GSK-3 phosphorylation of Threonines 222/226. BMC Mol Biol. 2006;7:14 pubmed..In short, we find no evidence that C/EBPalpha activity is regulated by direct phosphorylation by GSK3. ..
- Tong J, Li W, Vidal C, Yeo L, Fatkin D, Duque G. Lamin A/C deficiency is associated with fat infiltration of muscle and bone. Mech Ageing Dev. 2011;132:552-9 pubmed publisher..In conclusion, lamin A/C could constitute the determinant factor in the pathogenesis and potential treatment of both sarcopenia and osteopenia, which are commonly observed in the frailty syndrome. ..
- Poli V, Mancini F, Cortese R. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990;63:643-53 pubmed
- Vertino A, Taylor Jones J, Longo K, Bearden E, Lane T, McGehee R, et al. Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Mol Biol Cell. 2005;16:2039-48 pubmed..Thus, alteration in Wnt signaling in myoblasts with age may contribute to impaired muscle regenerative capacity and to increased muscle adiposity, both characteristic of aged muscle. ..
- Flodby P, Barlow C, Kylefjord H, Ahrlund Richter L, Xanthopoulos K. Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha. J Biol Chem. 1996;271:24753-60 pubmed..These results suggest a critical role for C/EBPalpha in vivo for the acquisition of terminally differentiated functions in liver including the maintenance of physiologic energy homeostasis. ..
- Liu J, Zhang Y, You R, Zeng F, Guo D, Wang K. Polysaccharide isolated from Angelica sinensis inhibits hepcidin expression in rats with iron deficiency anemia. J Med Food. 2012;15:923-9 pubmed publisher..The results indicate that ASP can suppress the expression of hepcidin in rats with IDA, and may be useful for the treatment of IDA. ..
- Tinel M, Berson A, Elkahwaji J, Cresteil T, Beaune P, Pessayre D. Downregulation of cytochromes P450 in growth-stimulated rat hepatocytes: role of c-Myc induction and impaired C/EBP binding to DNA. J Hepatol. 2003;39:171-8 pubmed..EGF overexpresses c-Myc, decreases C/EBP binding to DNA and downregulates CYPs. We suggest that c-Myc may form inactive complexes with C/EBPs, thus decreasing C/EBP-mediated CYP transactivation. ..
- Brouillette J, Quirion R. Transthyretin: a key gene involved in the maintenance of memory capacities during aging. Neurobiol Aging. 2008;29:1721-32 pubmed..Our study provides genetic, behavioural and molecular evidence that TTR is involved in the maintenance of normal cognitive processes during aging by acting on the retinoid signalling pathway. ..
- Martis P, Whitsett J, Xu Y, Perl A, Wan H, Ikegami M. C/EBPalpha is required for lung maturation at birth. Development. 2006;133:1155-64 pubmed..Deletion of the Cebpa gene in respiratory epithelial cells in fetal mice caused respiratory failure at birth...
- Chiang M, Chern Y, Juo C. The dysfunction of hepatic transcriptional factors in mice with Huntington's Disease. Biochim Biophys Acta. 2011;1812:1111-20 pubmed publisher..These findings show that the impairment of PPAR? contributes to the liver dysfunction observed in HD. Treatment with PPAR? agents (TZD and rosiglitazone) enhanced the function of PPAR?, and might lead to therapeutic benefits. ..
- Verga Falzacappa M, Vujic Spasic M, Kessler R, Stolte J, Hentze M, Muckenthaler M. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood. 2007;109:353-8 pubmed..These results identify a missing link in the acute-phase activation of hepcidin and establish STAT3 as a key effector of baseline hepcidin expression and during inflammatory conditions. ..
- Siegel A, Hays N, Day R. Unraveling transcription factor interactions with heterochromatin protein 1 using fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy. J Biomed Opt. 2013;18:25002 pubmed publisher..The functional significance of these interactions is discussed. ..
- Mason R, Pan T, Edeen K, Nielsen L, Zhang F, Longphre M, et al. Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells. J Clin Invest. 2003;112:244-55 pubmed..In summary, KGF stimulates lipogenesis in type II cells by a coordinated expression of lipogenic enzymes and transport proteins regulated by C/EBP isoforms and SREBP-1c. ..
- Ikeda H, Omoteyama K, Yoshida K, Nishi S, Sakai M. CCAAT enhancer-binding protein alpha suppresses the rat placental glutathione S-transferase gene in normal liver. J Biol Chem. 2006;281:6734-41 pubmed..These results indicate that C/EBPalpha is a negative regulator of GST-P gene expression in normal liver. ..
- Fong Y, Shen K, Chen L, Cheng J. Changes of CCAAT enhancer-binding proteins (CEBPs) in the lung of streptozotocin-induced diabetic rats. Horm Metab Res. 2011;43:261-7 pubmed publisher..The changes of expression of C/EBP? and C/EBP? are not caused by changes of osmolarity but by D-glucose itself. ..
- Timchenko N, Harris T, Wilde M, Bilyeu T, Burgess Beusse B, Finegold M, et al. CCAAT/enhancer binding protein alpha regulates p21 protein and hepatocyte proliferation in newborn mice. Mol Cell Biol. 1997;17:7353-61 pubmed
- Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez F, Talianidis I. Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006;20:2293-305 pubmed..The results illustrate the remarkable flexibility of a self-sustaining transcription factor network, built up by complex dominant and redundant regulatory motifs in developing hepatocytes. ..
- Pedersen T, Kowenz Leutz E, Leutz A, Nerlov C. Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation. Genes Dev. 2001;15:3208-16 pubmed