C/EBPalpha

Summary

Gene Symbol: C/EBPalpha
Description: CCAAT enhancer binding protein alpha
Alias: C/EBP-alpha, CEBP, CCAAT/enhancer-binding protein alpha, CCAAT/enhancer binding protein (C/EBP), alpha
Species: human
Products:     C/EBPalpha

Top Publications

  1. Shim M, Smart R. Lithium stabilizes the CCAAT/enhancer-binding protein alpha (C/EBPalpha) through a glycogen synthase kinase 3 (GSK3)-independent pathway involving direct inhibition of proteasomal activity. J Biol Chem. 2003;278:19674-81 pubmed
    ..These results demonstrate C/EBPalpha is degraded via a ubiquitin-dependent proteasomal pathway, and LiCl stabilizes C/EBPalpha through a GSK3-independent pathway involving direct inhibition of proteasome activity. ..
  2. Helbling D, Mueller B, Timchenko N, Schardt J, Eyer M, Betts D, et al. CBFB-SMMHC is correlated with increased calreticulin expression and suppresses the granulocytic differentiation factor CEBPA in AML with inv(16). Blood. 2005;106:1369-75 pubmed
    ..Inhibition of calreticulin by siRNA restored CEBPA levels. Our results suggest that modulation of CEBPA by calreticulin represents a novel mechanism involved in the differentiation block in CBFB-SMMHC AML. ..
  3. Wouters B, Louwers I, Valk P, Lowenberg B, Delwel R. A recurrent in-frame insertion in a CEBPA transactivation domain is a polymorphism rather than a mutation that does not affect gene expression profiling-based clustering of AML. Blood. 2007;109:389-90 pubmed
  4. Guibal F, Alberich Jorda M, Hirai H, Ebralidze A, Levantini E, Di Ruscio A, et al. Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia. Blood. 2009;114:5415-25 pubmed publisher
    ..Our findings provide further understanding of the biology of APL by demonstrating that a committed transformed progenitor can initiate and propagate the disease. ..
  5. Mizushima Y, Taki T, Shimada A, Yui Y, Hiraumi Y, Matsubara H, et al. Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype: a study by the Japanese Childhood AML Cooperative Study Group. Int J Hematol. 2010;91:831-7 pubmed publisher
    ..Thus, 1-5-6-8 isoform expression may be associated with an adverse prognosis in pediatric AML with normal karyotype. CEBPA mutations may indicate a favorable prognosis. ..
  6. Xue M, Li X, Wu W, Zhang S, Wu S, Li Z, et al. Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein ? contributes to bladder cancer cell growth and reduced apoptosis. Oncol Rep. 2014;31:1993-2000 pubmed publisher
  7. Ross S, Radomska H, Wu B, Zhang P, Winnay J, Bajnok L, et al. Phosphorylation of C/EBPalpha inhibits granulopoiesis. Mol Cell Biol. 2004;24:675-86 pubmed
    ..Thus, myeloid development is partly regulated by an ERK1/2-mediated change in the conformation of C/EBPalpha that favors monocyte differentiation by blocking granulopoiesis. ..
  8. Efimova T, Deucher A, Kuroki T, Ohba M, Eckert R. Novel protein kinase C isoforms regulate human keratinocyte differentiation by activating a p38 delta mitogen-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha. J Biol Chem. 2002;277:31753-60 pubmed
  9. Geletu M, Balkhi M, Peer Zada A, Christopeit M, Pulikkan J, Trivedi A, et al. Target proteins of C/EBPalphap30 in AML: C/EBPalphap30 enhances sumoylation of C/EBPalphap42 via up-regulation of Ubc9. Blood. 2007;110:3301-9 pubmed
    ..In summary, our data indicate that Ubc9 is an important C/EBPalphap30 target through which C/EBPalphap30 enhances the sumoylation of C/EBPalphap42 to inhibit granulocytic differentiation. ..

More Information

Publications92

  1. Pabst T, Mueller B, Harakawa N, Schoch C, Haferlach T, Behre G, et al. AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat Med. 2001;7:444-51 pubmed
    ..Conditional expression of C/EBPalpha in AML1-ETO-positive Kasumi-1 cells results in neutrophilic differentiation. We suggest that restoring C/EBPalpha expression will have therapeutic implications in RUNX1-CBF2T1-positive leukemias. ..
  2. 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 pubmed
    ..Ours is the first report of CEBPA mutations in human neoplasia, and such mutations are likely to induce the differentiation block found in AML. ..
  3. Reddy S, Pakala S, Ohshiro K, Rayala S, Kumar R. MicroRNA-661, a c/EBPalpha target, inhibits metastatic tumor antigen 1 and regulates its functions. Cancer Res. 2009;69:5639-42 pubmed publisher
    ..Based on these findings, we suggest that miR-661 be further investigated for therapeutic use in down-regulating the expression of MTA1 in cancer cells. ..
  4. Fröhling S, Schlenk R, Stolze I, Bihlmayr J, Benner A, Kreitmeier S, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol. 2004;22:624-33 pubmed
    ..Mutant CEBPA predicts favorable prognosis and may improve risk stratification in AML patients with normal cytogenetics. ..
  5. Schlenk R, Dohner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909-18 pubmed publisher
    ..Genotypes defined by the mutational status of NPM1, FLT3, CEBPA, and MLL are associated with the outcome of treatment for patients with cytogenetically normal AML. ..
  6. Pabst T, Eyholzer M, Haefliger S, Schardt J, Mueller B. Somatic CEBPA mutations are a frequent second event in families with germline CEBPA mutations and familial acute myeloid leukemia. J Clin Oncol. 2008;26:5088-93 pubmed publisher
    ..Our data strongly indicate that germline CEBPA mutations predispose to AML and that additional somatic CEBPA mutations contribute to the development of the disease. ..
  7. Park S, Chi H, Cho Y, Jang S, Park C. CEBPA single mutation can be a possible favorable prognostic indicator in NPM1 and FLT3-ITD wild-type acute myeloid leukemia patients with intermediate cytogenetic risk. Leuk Res. 2013;37:1488-94 pubmed publisher
  8. Bengoechea Alonso M, Ericsson J. The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBPalpha for degradation. Proc Natl Acad Sci U S A. 2010;107:11817-22 pubmed publisher
    ..Thus, Fbxw7 could be an important regulator of energy and lipid metabolism. ..
  9. Matsushita H, Nakajima H, Nakamura Y, Tsukamoto H, Tanaka Y, Jin G, et al. C/EBPalpha and C/EBPvarepsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. Oncogene. 2008;27:6749-60 pubmed publisher
  10. Tavor S, Park D, Gery S, Vuong P, Gombart A, Koeffler H. Restoration of C/EBPalpha expression in a BCR-ABL+ cell line induces terminal granulocytic differentiation. J Biol Chem. 2003;278:52651-9 pubmed
  11. Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis M, Nervi C, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell. 2005;123:819-31 pubmed
    ..Altogether, our data indicate that miR-223 plays a crucial role during granulopoiesis and point to the NFI-A repression as an important molecular pathway mediating gene reprogramming in this cell lineage. ..
  12. 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. ..
  13. Choi B, Park G, Rho H. Interaction of hepatitis B viral X protein and CCAAT/ enhancer-binding protein alpha synergistically activates the hepatitis B viral enhancer II/pregenomic promoter. J Biol Chem. 1999;274:2858-65 pubmed
    ..These results suggest that the interaction of HBx and C/EBPalpha enhances the transcription of the HBV pregenomic promoter for the effective life cycle of HBV in hepatocytes. ..
  14. Wang N, Finegold M, Bradley A, Ou C, Abdelsayed S, Wilde M, et al. Impaired energy homeostasis in C/EBP alpha knockout mice. Science. 1995;269:1108-12 pubmed
    ..This study demonstrates that C/EBP alpha is critical for the establishment and maintenance of energy homeostasis in neonates. ..
  15. Fuchs O, Provaznikova D, Kocova M, Kostecka A, Cvekova P, Neuwirtova R, et al. CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin's lymphoma. Blood Cells Mol Dis. 2008;40:401-5 pubmed publisher
    ..No C/EBPalpha mutations were detected in healthy donors (41 individuals). We discuss how these mutations can affect the cellular function of C/EBPalpha and block the myeloid differentiation. ..
  16. Yeamans C, Wang D, Paz Priel I, Torbett B, Tenen D, Friedman A. C/EBPalpha binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood. 2007;110:3136-42 pubmed
    ..1(+/+), PU.1(+/-), or PU.1(+/kd) marrow myeloid progenitors but induces granulocyte lineage commitment in PU.1(kd/kd) cells lacking the PU.1 distal enhancer and does not induce either lineage in PU.1(-/-) cells. ..
  17. Pabst T, Mueller B. Complexity of CEBPA dysregulation in human acute myeloid leukemia. Clin Cancer Res. 2009;15:5303-7 pubmed publisher
    The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is crucial for normal development of granulocytes...
  18. Schmidt D, Wilson M, Ballester B, Schwalie P, Brown G, Marshall A, et al. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science. 2010;328:1036-40 pubmed publisher
    ..Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution. ..
  19. Taskesen E, Bullinger L, Corbacioglu A, Sanders M, Erpelinck C, Wouters B, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011;117:2469-75 pubmed publisher
    ..Based on these findings, we propose that CEBPA(dm) should be clearly defined from CEBPA(sm) AML and considered as a separate entity in the classification of AML. ..
  20. Kim S, Kim D, Jang J, Jung C, Jang M, Ki C, et al. Novel mutations in CEBPA in Korean Patients with acute myeloid leukemia with a normal karyotype. Ann Lab Med. 2012;32:153-7 pubmed publisher
    ..Long-term follow-up data from a larger series of patients with comprehensive molecular profiling are needed to delineate the prognostic implications. ..
  21. Leroy H, Roumier C, Huyghe P, Biggio V, Fenaux P, Preudhomme C. CEBPA point mutations in hematological malignancies. Leukemia. 2005;19:329-34 pubmed
    ..Systematic analysis of CEBPA mutations, in addition to that of alterations in master genes of hematopoiesis, may be useful to assess the prognosis of AML particularly in patients belonging to the 'intermediate' prognostic subgroup. ..
  22. Trivedi A, Bararia D, Christopeit M, Peerzada A, Singh S, Kieser A, et al. Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPalpha by inhibiting its ubiquitination. Oncogene. 2007;26:1789-801 pubmed
    ..Thus, we report the first proteomic screen of C/EBP-interacting proteins, which identifies JNK1 as positive regulator of C/EBPalpha. ..
  23. Wu Z, Rosen E, Brun R, Hauser S, Adelmant G, Troy A, et al. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 1999;3:151-8 pubmed
    ..These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage. ..
  24. Barjesteh van Waalwijk van Doorn Khosrovani S, Erpelinck C, Meijer J, van Oosterhoud S, van Putten W, Valk P, et al. Biallelic mutations in the CEBPA gene and low CEBPA expression levels as prognostic markers in intermediate-risk AML. Hematol J. 2003;4:31-40 pubmed
    ..By including this newly developed PCR assay, we define a subgroup of good-risk patients within the heterogeneous intermediate-risk group of AML. ..
  25. Ho P, Alonzo T, Gerbing R, Pollard J, Stirewalt D, Hurwitz C, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2009;113:6558-66 pubmed publisher
    ..24, P = .047). As CEBPA mutations are associated with lower relapse rate and improved survival, CEBPA mutation analysis needs to be incorporated into initial screening for risk identification and therapy allocation at diagnosis...
  26. Marcucci G, Maharry K, Radmacher M, Mrozek K, Vukosavljevic T, Paschka P, et al. Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a Cancer and Leukemia Group B Study. J Clin Oncol. 2008;26:5078-87 pubmed publisher
    ..The gene and miRNA expression profiling provided insights into leukemogenesis of the CN-AML molecular high-risk group, indicating that CEBPA mutations are associated with partial erythroid differentiation. ..
  27. Choy L, Derynck R. Transforming growth factor-beta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J Biol Chem. 2003;278:9609-19 pubmed
    ..Smad3/4 did not reduce the ability of C/EBP to bind to its cognate DNA sequence, but repressed transcription by inhibiting the transactivation function of C/EBP. ..
  28. Green C, Koo K, Hills R, Burnett A, Linch D, Gale R. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol. 2010;28:2739-47 pubmed publisher
    ..Screening for CEBPA mutations can be restricted to patients with intermediate-risk cytogenetics lacking an FLT3/ITD or NPM1 mutation. Only the presence of a CEBPA-double mutation should be used for therapy risk stratification. ..
  29. Pulikkan J, Peramangalam P, Dengler V, Ho P, Preudhomme C, Meshinchi S, et al. C/EBP? regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations. Blood. 2010;116:5638-49 pubmed publisher
    The transcription factor, CCAAT enhancer binding protein alpha (C/EBP?), is crucial for granulopoiesis and is deregulated by various mechanisms in acute myeloid leukemia (AML)...
  30. Biggio V, Renneville A, Nibourel O, Philippe N, Terriou L, Roumier C, et al. Recurrent in-frame insertion in C/EBPalpha TAD2 region is a polymorphism without prognostic value in AML. Leukemia. 2008;22:655-7 pubmed
  31. Cao Z, Umek R, McKnight S. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991;5:1538-52 pubmed
    ..The temporal pattern of expression of these three C/EBP isoforms during adipocyte differentiation may reflect the underpinnings of a regulatory cascade that controls the process of terminal cell differentiation. ..
  32. Wouters B, Jorda M, Keeshan K, Louwers I, Erpelinck Verschueren C, Tielemans D, et al. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood. 2007;110:3706-14 pubmed
    ..A gene expression prediction signature allowed the detection of similar cases of leukemia in independent series of AML. ..
  33. Lin T, Hou H, Chou W, Ou D, Yu S, Tien H, et al. CEBPA methylation as a prognostic biomarker in patients with de novo acute myeloid leukemia. Leukemia. 2011;25:32-40 pubmed publisher
    ..416; 95% confidence interval, 0.223-0.777, P=0.006) and OS (hazard ratio=0.406; 95% confidence interval, 0.166-0.996, P=0.050). We conclude that CEBPA methylation status is a useful prognostic biomarker for AML patients. ..
  34. Tada Y, Brena R, Hackanson B, Morrison C, Otterson G, Plass C. Epigenetic modulation of tumor suppressor CCAAT/enhancer binding protein alpha activity in lung cancer. J Natl Cancer Inst. 2006;98:396-406 pubmed
    ..DNA hypermethylation of the upstream C/EBPalpha promoter region, not the core promoter region as previously reported, is critical in the regulation of C/EBPalpha expression in human lung cancer. ..
  35. Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler W, et al. C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4. Mol Cell. 2001;8:817-28 pubmed
    ..Our data demonstrate that the liver-specific transcription factor C/EBPalpha brings about growth arrest through direct inhibition of cdk2 and cdk4. ..
  36. Dufour A, Schneider F, Hoster E, Benthaus T, Ksienzyk B, Schneider S, et al. Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients. Ann Hematol. 2012;91:1051-63 pubmed publisher
    ..Confirmation of these results in larger studies will clarify whether an additional moCEBPA mutation influences the risk stratification of patients with an NPM1 mutated/FLT3-ITD positive genotype. ..
  37. Wang G, Timchenko N. Dephosphorylated C/EBPalpha accelerates cell proliferation through sequestering retinoblastoma protein. Mol Cell Biol. 2005;25:1325-38 pubmed
    ..Our data demonstrate a new pathway by which the phosphorylation-dependent switch of biological functions of C/EBPalpha promotes liver proliferation. ..
  38. Chapiro E, Russell L, Radford Weiss I, Bastard C, Lessard M, Struski S, et al. Overexpression of CEBPA resulting from the translocation t(14;19)(q32;q13) of human precursor B acute lymphoblastic leukemia. Blood. 2006;108:3560-3 pubmed
    ..Overexpression of apparently normal CEBPA RNA or protein was observed in 6 patients. These data indicate that CEBPA may exhibit oncogenic as well as tumor suppressor properties in human leukemogenesis. ..
  39. 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. ..
  40. Sato A, Yamada N, Ogawa Y, Ikegami M. CCAAT/enhancer-binding protein-? suppresses lung tumor development in mice through the p38? MAP kinase pathway. PLoS ONE. 2013;8:e57013 pubmed publisher
    ..of C/EBP? in lung tumors in vivo using transgenic mice with lung epithelial specific conditional deletion of Cebpa (Cebp?(?/?) mice) and a urethane-induced lung tumor model...
  41. Eyholzer M, Schmid S, Wilkens L, Mueller B, Pabst T. The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML. Br J Cancer. 2010;103:275-84 pubmed publisher
    ..Our data provide a rationale for miR-29b suppression in AML patients with loss of chromosome 7q or CEBPA deficiency. ..
  42. Fasan A, Haferlach C, Alpermann T, Jeromin S, Grossmann V, Eder C, et al. The role of different genetic subtypes of CEBPA mutated AML. Leukemia. 2014;28:794-803 pubmed publisher
    ..020). Outcome in CEBPAsm cases strongly depended on concurrent FLT3-ITD. In conclusion, we propose that only CEBPAdm should be considered as an entity in the WHO classification of AML and should be clearly distinguished from CEBPAsm AML. ..
  43. Yin H, Lowery M, Glass J. In prostate cancer C/EBPalpha promotes cell growth by the loss of interactions with CDK2, CDK4, and E2F and by activation of AKT. Prostate. 2009;69:1001-16 pubmed publisher
    ..AKT and PPA2 inhibitors restored both the anti-proliferation function of C/EBPalpha and the interaction between C/EBPalpha and E2F1/E2F4. In prostate cancer cells C/EBPalpha cannot function as a tumor suppressor. ..
  44. Lin F, MacDougald O, Diehl A, Lane M. A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity. Proc Natl Acad Sci U S A. 1993;90:9606-10 pubmed
    ..During differentiation of 3T3-L1 preadipocytes and during hepatocyte development, the cellular p42C/EBP alpha/p30C/EBP alpha ratio changes, raising the possibility of a regulatory role. ..
  45. Dufour A, Schneider F, Metzeler K, Hoster E, Schneider S, Zellmeier E, et al. Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol. 2010;28:570-7 pubmed publisher
    ..These findings are of great significance for risk-adapted therapeutic strategies in AML. ..
  46. Muller C, Bremer A, Schreiber S, Eichwald S, Calkhoven C. Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA transcription and cell size. EMBO J. 2010;29:897-909 pubmed publisher
    ..Altogether, our results suggest that control of rRNA synthesis is a novel function of C/EBPalpha adding to its role as key regulator of cell growth and proliferation...
  47. Erickson R, Hemati N, Ross S, MacDougald O. p300 coactivates the adipogenic transcription factor CCAAT/enhancer-binding protein alpha. J Biol Chem. 2001;276:16348-55 pubmed
    ..Analyses using C/EBPalpha conserved region mutants suggest that multiple regions (CR2 and CR3) of the C/EBPalpha transactivation domain functionally interact with p300. ..
  48. Halmos B, Huettner C, Kocher O, Ferenczi K, Karp D, Tenen D. Down-regulation and antiproliferative role of C/EBPalpha in lung cancer. Cancer Res. 2002;62:528-34 pubmed
    ..Genetic analysis of the C/EBPalpha gene is in progress to fully evaluate its role as a novel tumor suppressor in lung cancer. ..
  49. Kato N, Kitaura J, Doki N, Komeno Y, Watanabe Okochi N, Togami K, et al. Two types of C/EBP? mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models. Blood. 2011;117:221-33 pubmed publisher
    ..1, despite low expression levels of p30 protein generated by C/EBP?-N(m). Thus, 2 types of C/EBP? mutations are implicated in leukemo-genesis, involving different and cooperating molecular mechanisms. ..
  50. Timchenko N, Wilde M, Darlington G. C/EBPalpha regulates formation of S-phase-specific E2F-p107 complexes in livers of newborn mice. Mol Cell Biol. 1999;19:2936-45 pubmed
    ..The disruption of E2F-p107 complexes correlates with C/EBPalpha-mediated growth arrest of hepatocytes in newborn animals. ..
  51. Hollink I, van den Heuvel Eibrink M, Arentsen Peters S, Zimmermann M, Peeters J, Valk P, et al. Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia. Haematologica. 2011;96:384-92 pubmed publisher
    ..Furthermore, clustering of gene expression profiles provided insight into the biological similarities and diversities of the different aberrations in CEBPA in pediatric acute myeloid leukemia. ..
  52. Zeng C, Wang R, Li D, Lin X, Wei Q, Yuan Y, et al. A novel GSK-3 beta-C/EBP alpha-miR-122-insulin-like growth factor 1 receptor regulatory circuitry in human hepatocellular carcinoma. Hepatology. 2010;52:1702-12 pubmed publisher
    ..Moreover, AFB? exposure resulted in decreased activity in GSK-3?, C/EBP?, and miR-122 and increased levels of IGF-1R, whereas restoration of miR-122 suppressed the tumorigenicity of HCC and AFB?-transformed cells...
  53. Renneville A, Boissel N, Gachard N, Naguib D, Bastard C, De Botton S, et al. The favorable impact of CEBPA mutations in patients with acute myeloid leukemia is only observed in the absence of associated cytogenetic abnormalities and FLT3 internal duplication. Blood. 2009;113:5090-3 pubmed publisher
    ..7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1.01-8.2; with P = .034 and .05, for abnormal karyotype and FLT3-ITD, respectively). ..
  54. D Alo F, Johansen L, Nelson E, Radomska H, Evans E, Zhang P, et al. The amino terminal and E2F interaction domains are critical for C/EBP alpha-mediated induction of granulopoietic development of hematopoietic cells. Blood. 2003;102:3163-71 pubmed
    ..These results further emphasize the importance of inhibition of proliferative pathways in granulopoiesis and demonstrate that several regions of the C/EBP alpha protein are involved in this mechanism. ..
  55. Singh S, Trivedi A, Behre G. C/EBPalpha S248A mutation reduces granulocytic differentiation in human leukemic K562 cells. Biochem Biophys Res Commun. 2008;369:692-4 pubmed publisher
    ..Based on our observations in the present study, we conclude that S248A mutation of C/EBPalpha leads to a reduction of granulocytic differentiation markers and a block in differentiation at the morphological level. ..
  56. Snaddon J, Smith M, Neat M, Cambal Parrales M, Dixon McIver A, Arch R, et al. Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2. Genes Chromosomes Cancer. 2003;37:72-8 pubmed
    ..In conclusion, mutation of CEBPA is a recurrent finding in AML and appears specific to the intermediate cytogenetic risk group patients. ..
  57. Jost E, do O N, Wilop S, Herman J, Osieka R, Galm O. Aberrant DNA methylation of the transcription factor C/EBPalpha in acute myelogenous leukemia. Leuk Res. 2009;33:443-9 pubmed publisher
    ..Our results provide further evidence for epigenetic dysregulation of C/EBPalpha in AML. ..
  58. Subramanian L, Benson M, INIGUEZ LLUHI J. A synergy control motif within the attenuator domain of CCAAT/enhancer-binding protein alpha inhibits transcriptional synergy through its PIASy-enhanced modification by SUMO-1 or SUMO-3. J Biol Chem. 2003;278:9134-41 pubmed
  59. Smith M, Cavenagh J, Lister T, Fitzgibbon J. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004;351:2403-7 pubmed
    ..All three patients are currently well, with no abnormalities in the bone marrow. CEBPA mutation is apparently the primary event in the development of AML in this family. ..
  60. Dhawan P, Wieder R, Weider R, Christakos S. CCAAT enhancer-binding protein alpha is a molecular target of 1,25-dihydroxyvitamin D3 in MCF-7 breast cancer cells. J Biol Chem. 2009;284:3086-95 pubmed publisher
    ..These findings also identify C/EBPalpha as a 1,25(OH)(2)D(3) target in breast cancer cells and provide evidence for C/EBPalpha as a candidate for breast cancer treatment. ..
  61. Wouters B, Lowenberg B, Erpelinck Verschueren C, van Putten W, Valk P, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113:3088-91 pubmed publisher
    ..These results demonstrate significant underlying heterogeneity within CEBPA mutation-positive AML with prognostic relevance. ..
  62. Yoon K, Smart R. C/EBPalpha is a DNA damage-inducible p53-regulated mediator of the G1 checkpoint in keratinocytes. Mol Cell Biol. 2004;24:10650-60 pubmed
    ..Our results uncover a novel role for C/EBPalpha as a p53-regulated DNA damage-inducible gene that has a critical function in the DNA damage G(1) checkpoint response in keratinocytes. ..
  63. 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
  64. Lin L, Chen C, Lin D, Tsay W, Tang J, Yeh Y, et al. Characterization of CEBPA mutations in acute myeloid leukemia: most patients with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells. Clin Cancer Res. 2005;11:1372-9 pubmed
  65. Calkhoven C, Bouwman P, Snippe L, Ab G. Translation start site multiplicity of the CCAAT/enhancer binding protein alpha mRNA is dictated by a small 5' open reading frame. Nucleic Acids Res. 1994;22:5540-7 pubmed
    ..The presence of a similar, thusfar unnoticed, small ORF 5' to the major initiation codon of C/EBP beta mRNA suggests that start site multiplicity from this mRNA may be governed by the same mechanism. ..
  66. Grandinetti K, Stevens T, Ha S, Salamone R, Walker J, Zhang J, et al. Overexpression of TRIB2 in human lung cancers contributes to tumorigenesis through downregulation of C/EBP?. Oncogene. 2011;30:3328-35 pubmed publisher
    ..Together, these data identify TRIB2 as a potential driver of lung tumorigenesis through a mechanism that involves downregulation of C/EBP?. ..
  67. 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. ..
  68. Nookala A, Shah A, Noel R, Kumar A. HIV-1 Tat-mediated induction of CCL5 in astrocytes involves NF-?B, AP-1, C/EBP? and C/EBP? transcription factors and JAK, PI3K/Akt and p38 MAPK signaling pathways. PLoS ONE. 2013;8:e78855 pubmed publisher
    ..This was further confirmed at transcriptional level that AP-1, C/EBP? and C/EBP? were involved in CCL5 up-regulation. ..
  69. Wang S, Wu F, Yu Y, Hayward G. CCAAT/enhancer-binding protein-alpha is induced during the early stages of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic cycle reactivation and together with the KSHV replication and transcription activator (RTA) cooperatively stimulates the v. J Virol. 2003;77:9590-612 pubmed
  70. 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
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    ..Our study suggests that methylation testing may be as important as mutation testing for identifying AML cases with CEBPA dysregulation and may be indicated in the routine prognostic workup of AML. ..
  72. Iakova P, Awad S, Timchenko N. Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell. 2003;113:495-506 pubmed
  73. Hackanson B, Bennett K, Brena R, Jiang J, Claus R, Chen S, et al. Epigenetic modification of CCAAT/enhancer binding protein alpha expression in acute myeloid leukemia. Cancer Res. 2008;68:3142-51 pubmed publisher
    ..Our results indicate that epigenetic alterations of C/EBP alpha are a frequent event in AML and that epigenetic treatment can result in down-regulation of a key hematopoietic transcription factor. ..
  74. Behre G, Singh S, Liu H, Bortolin L, Christopeit M, Radomska H, et al. Ras signaling enhances the activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation of serine 248. J Biol Chem. 2002;277:26293-9 pubmed
    ..These data suggest a model where Ras signaling enhances the activity of C/EBP alpha to induce granulocytic differentiation by phosphorylation of serine 248. ..
  75. Pabst T, Eyholzer M, Fos J, Mueller B. Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis. Br J Cancer. 2009;100:1343-6 pubmed publisher
    ..In a multivariable analysis, only double -- but not single -- CEBPA mutations were identified as independent prognostic factors. These findings indicate heterogeneity within AML patients with CEBPA mutations. ..
  76. Gombart A, Hofmann W, Kawano S, Takeuchi S, Krug U, Kwok S, et al. Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein alpha in myelodysplastic syndromes and acute myeloid leukemias. Blood. 2002;99:1332-40 pubmed
    ..These results suggest that mutation of C/EBPalpha is involved in specific subtypes of AML and in MDS, but may occur rarely in other types of leukemias or nonhematologic malignancies. ..
  77. Lu G, Leung C, Yan B, Tan C, Low S, Aung M, et al. C/EBPalpha is up-regulated in a subset of hepatocellular carcinomas and plays a role in cell growth and proliferation. Gastroenterology. 2010;139:632-43, 643.e1-4 pubmed publisher
    ..C/EBPalpha is up-regulated in a subset of HCCs and has growth-promoting activities in HCC cells. Novel oncogenic mechanisms involving C/EBPalpha may be amenable to epigenetic regulation to improve treatment outcomes. ..
  78. Zhang S, Jiang T, Feng L, Sun J, Lu H, Wang Q, et al. Yin Yang-1 suppresses differentiation of hepatocellular carcinoma cells through the downregulation of CCAAT/enhancer-binding protein alpha. J Mol Med (Berl). 2012;90:1069-77 pubmed publisher
    ..In summary, our study demonstrated that YY1 could promote hepatocellular carcinogenesis and inhibit cellular differentiation through the downregulation of CEBPA expression. ..
  79. Kumagai T, Akagi T, Desmond J, Kawamata N, Gery S, Imai Y, et al. Epigenetic regulation and molecular characterization of C/EBPalpha in pancreatic cancer cells. Int J Cancer. 2009;124:827-33 pubmed publisher
  80. Eyholzer M, Schmid S, Schardt J, Haefliger S, Mueller B, Pabst T. Complexity of miR-223 regulation by CEBPA in human AML. Leuk Res. 2010;34:672-6 pubmed publisher
    ..Our results suggest that miR-223 suppression in AML is caused by impaired miR-223 upstream factors. ..
  81. Lincoln A, Monczak Y, Williams S, Johnson P. Inhibition of CCAAT/enhancer-binding protein alpha and beta translation by upstream open reading frames. J Biol Chem. 1998;273:9552-60 pubmed
    ..Our data indicate that the uORFs regulate translation of full-length C/EBPalpha and C/EBPbeta and do not play a role in generating truncated forms of these proteins, as has been suggested by start site multiplicity models. ..
  82. Preudhomme C, Sagot C, Boissel N, Cayuela J, Tigaud I, De Botton S, et al. Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood. 2002;100:2717-23 pubmed
    ..We thus propose a risk classification that includes in the favorable subgroup all patients from the intermediate subgroup displaying CEBPA mutations when not associated with FLT3-ITD. ..