ccaat enhancer binding protein beta


Summary: A CCAAT-enhancer-binding protein found in LIVER; INTESTINES; LUNG and ADIPOSE TISSUE. It is an important mediator of INTERLEUKIN-6 signaling.

Top Publications

  1. Mantena S, Kannan A, Cheon Y, Li Q, Johnson P, Bagchi I, et al. C/EBPbeta is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma. Proc Natl Acad Sci U S A. 2006;103:1870-5 pubmed
    ..Collectively, our studies established that C/EBPbeta is a key mediator of steroid responsiveness of the epithelium and stroma in the mouse uterus. ..
  2. Li X, Kim J, Grønborg M, Urlaub H, Lane M, Tang Q. Role of cdk2 in the sequential phosphorylation/activation of C/EBPbeta during adipocyte differentiation. Proc Natl Acad Sci U S A. 2007;104:11597-602 pubmed
    ..Thus, MAPK and cdk2/cyclinA act sequentially to maintain Thr(188) of C/EBPbeta in the primed phosphorylated state during MCE and thereby progression of terminal differentiation. ..
  3. Grimm S, Contreras A, Barcellos Hoff M, Rosen J. Cell cycle defects contribute to a block in hormone-induced mammary gland proliferation in CCAAT/enhancer-binding protein (C/EBPbeta)-null mice. J Biol Chem. 2005;280:36301-9 pubmed
    ..Collectively, these changes prevent C/EBPbeta-null mammary epithelial cells from responding to hormone-induced proliferative signals. ..
  4. Uldry M, Yang W, St Pierre J, Lin J, Seale P, Spiegelman B. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab. 2006;3:333-41 pubmed
  5. Zwergal A, Quirling M, Saugel B, Huth K, Sydlik C, Poli V, et al. C/EBP beta blocks p65 phosphorylation and thereby NF-kappa B-mediated transcription in TNF-tolerant cells. J Immunol. 2006;177:665-72 pubmed
    ..These results define a new molecular mechanism responsible for TNF tolerance in monocytic cells that may contribute to the unresponsiveness seen in patients with sepsis. ..
  6. Barber S, Gama L, Dudaronek J, Voelker T, Tarwater P, Clements J. Mechanism for the establishment of transcriptional HIV latency in the brain in a simian immunodeficiency virus-macaque model. J Infect Dis. 2006;193:963-70 pubmed
    ..The brain is considered to be a reservoir of latent human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). We examined the mechanism by which innate immune responses contribute to the establishment of this reservoir...
  7. Shirakawa K, Maeda S, Gotoh T, Hayashi M, Shinomiya K, Ehata S, et al. CCAAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation. Mol Cell Biol. 2006;26:6105-16 pubmed
    ..Thus, endogenous CHOP may have dual roles in regulating osteoblast differentiation and bone formation. ..
  8. Li H, Gade P, Xiao W, KALVAKOLANU D. The interferon signaling network and transcription factor C/EBP-beta. Cell Mol Immunol. 2007;4:407-18 pubmed
    ..Here we describe the non-STAT pathways that participate in IFN-induced responses. In particular, we will focus on the role played by transcription factor C/EBP-beta in mediating these responses. ..
  9. Tominaga H, Maeda S, Hayashi M, Takeda S, Akira S, Komiya S, et al. CCAAT/enhancer-binding protein beta promotes osteoblast differentiation by enhancing Runx2 activity with ATF4. Mol Biol Cell. 2008;19:5373-86 pubmed publisher
    ..Thus, our results provide evidence that C/EBPbeta is a crucial cofactor in the promotion of osteoblast maturation by Runx2 and ATF4. ..

More Information


  1. Paquin A, Barnabe Heider F, Kageyama R, Miller F. CCAAT/enhancer-binding protein phosphorylation biases cortical precursors to generate neurons rather than astrocytes in vivo. J Neurosci. 2005;25:10747-58 pubmed
    ..Thus, activation of an MEK-C/EBP pathway in cortical precursors in vivo biases them to become neurons and against becoming astrocytes, thereby acting as a growth factor-regulated switch. ..
  2. Bezy O, Vernochet C, Gesta S, Farmer S, Kahn C. TRB3 blocks adipocyte differentiation through the inhibition of C/EBPbeta transcriptional activity. Mol Cell Biol. 2007;27:6818-31 pubmed
    ..Thus, TRB3 is an important negative regulator of adipogenesis that acts at an early step in the differentiation cascade to block the C/EBPbeta proadipogenic function. ..
  3. Wang W, Lee Y, Yang W, Chang W, Wang J. Sumoylation of LAP1 is involved in the HDAC4-mediated repression of COX-2 transcription. Nucleic Acids Res. 2008;36:6066-79 pubmed publisher
    ..In light of the above, our data suggest that the suCEBPD and suLAP1 are involved in the repression of COX-2 transcription through the recruitment of HDAC4. ..
  4. Staiger J, Lueben M, Berrigan D, Malik R, Perkins S, Hursting S, et al. C/EBPbeta regulates body composition, energy balance-related hormones and tumor growth. Carcinogenesis. 2009;30:832-40 pubmed publisher
    ..Thus, C/EBPbeta contributes to endocrine expression of IGF-1, leptin and insulin, which modulate energy balance and can contribute to cancer progression by creating a favorable environment for tumor cell proliferation and survival. ..
  5. Hirai H, Zhang P, Dayaram T, Hetherington C, Mizuno S, Imanishi J, et al. C/EBPbeta is required for 'emergency' granulopoiesis. Nat Immunol. 2006;7:732-9 pubmed
    ..C/EBPbeta inhibited proliferation less severely than did C/EBPalpha. These data suggest a critical function for C/EBPbeta in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors...
  6. Hirata M, Kugimiya F, Fukai A, Ohba S, Kawamura N, Ogasawara T, et al. C/EBPbeta Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57. PLoS ONE. 2009;4:e4543 pubmed publisher
  7. Marcinkowska E, Garay E, Gocek E, Chrobak A, Wang X, Studzinski G. Regulation of C/EBPbeta isoforms by MAPK pathways in HL60 cells induced to differentiate by 1,25-dihydroxyvitamin D3. Exp Cell Res. 2006;312:2054-65 pubmed
  8. Chen Z, Torrens J, Anand A, Spiegelman B, Friedman J. Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab. 2005;1:93-106 pubmed
    ..These data indicate that Krox20 is necessary for adipogenesis and that, when overexpressed, Krox20 potently stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. ..
  9. Raymond L, Eck S, Mollmark J, Hays E, Tomek I, Kantor S, et al. Interleukin-1 beta induction of matrix metalloproteinase-1 transcription in chondrocytes requires ERK-dependent activation of CCAAT enhancer-binding protein-beta. J Cell Physiol. 2006;207:683-8 pubmed
    ..Our findings demonstrate a novel role for C/EBP-beta in IL-1beta-induced connective tissue disease and define a new nuclear target for the ERK pathway in MMP-1 gene activation. ..
  10. Kortum R, Costanzo D, Haferbier J, Schreiner S, Razidlo G, Wu M, et al. The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis. Mol Cell Biol. 2005;25:7592-604 pubmed
    ..Titration of KSR1 expression reveals how a molecular scaffold can modulate the intensity and duration of signaling emanating from a single pathway to dictate cell fate. ..
  11. Yoon K, Zhu S, Ewing S, Smart R. Decreased survival of C/EBP beta-deficient keratinocytes is due to aberrant regulation of p53 levels and function. Oncogene. 2007;26:360-7 pubmed
  12. Berberich Siebelt F, Berberich I, Andrulis M, Santner Nanan B, Jha M, Klein Hessling S, et al. SUMOylation interferes with CCAAT/enhancer-binding protein beta-mediated c-myc repression, but not IL-4 activation in T cells. J Immunol. 2006;176:4843-51 pubmed
    ..These results suggest an important role of sumoylation in adjusting the finely tuned balance between proliferation and differentiation in peripheral T cells which is controlled by C/EBPbeta. ..
  13. Sebastian T, Johnson P. Stop and go: anti-proliferative and mitogenic functions of the transcription factor C/EBPbeta. Cell Cycle. 2006;5:953-7 pubmed
    ..Here we review the evidence for positive and negative cell cycle regulation by C/EBPbeta and discuss possible mechanisms by which this transcription factor could participate in both cellular senescence and oncogenic transformation. ..
  14. Pless O, Kowenz Leutz E, Knoblich M, Lausen J, Beyermann M, Walsh M, et al. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta. J Biol Chem. 2008;283:26357-63 pubmed publisher
    ..Our data identify C/EBPbeta as a direct substrate of G9a-mediated post-translational modification that alters the functional properties of C/EBPbeta during gene regulation. ..
  15. Smink J, Begay V, Schoenmaker T, Sterneck E, de Vries T, Leutz A. Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis through MafB. EMBO J. 2009;28:1769-81 pubmed publisher
    ..These data show that mTOR regulates osteoclast formation by modulating the C/EBPbeta isoform ratio, which in turn affects osteoclastogenesis by regulating MafB expression. ..
  16. Fan H, Liu Z, Shimada M, Sterneck E, Johnson P, Hedrick S, et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science. 2009;324:938-41 pubmed publisher
    ..Thus, ERK1/2 and C/EBPbeta constitute an in vivo LH-regulated signaling pathway that controls ovulation- and luteinization-related events. ..
  17. Tanaka N, Hoshino Y, Gold J, Hoshino S, Martiniuk F, Kurata T, et al. Interleukin-10 induces inhibitory C/EBPbeta through STAT-3 and represses HIV-1 transcription in macrophages. Am J Respir Cell Mol Biol. 2005;33:406-11 pubmed
    ..Only macrophages are able to repress HIV-1 LTR promoter activity and inhibit viral replication in response to IL-10 or type I IFN. ..
  18. Ewing S, Zhu S, Zhu F, House J, Smart R. C/EBPbeta represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19(Arf). Cell Death Differ. 2008;15:1734-44 pubmed publisher
  19. Tang Q, Grønborg M, Huang H, Kim J, Otto T, Pandey A, et al. Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and glycogen synthase kinase 3beta is required for adipogenesis. Proc Natl Acad Sci U S A. 2005;102:9766-71 pubmed
    ..The delayed transactivation of the C/EBPalpha and PPARgamma genes by C/EBPbeta appears necessary to allow mitotic clonal expansion, which would otherwise be prevented, because C/EBPalpha and PPARgamma are antimitotic. ..
  20. Wang G, Salisbury E, Shi X, Timchenko L, Medrano E, Timchenko N. HDAC1 promotes liver proliferation in young mice via interactions with C/EBPbeta. J Biol Chem. 2008;283:26179-87 pubmed publisher
    ..Thus, these studies have identified a new pathway that promotes liver proliferation in young mice and might contribute to the malignant transformations in the liver. ..
  21. Spooner C, Guo X, Johnson P, Schwartz R. Differential roles of C/EBP beta regulatory domains in specifying MCP-1 and IL-6 transcription. Mol Immunol. 2007;44:1384-92 pubmed
    ..LIP, the naturally occurring truncated form of C/EBPbeta, largely retains these regulatory domains and stimulates IL-6 but not MCP-1 transcription. ..
  22. Dudaronek J, Barber S, Clements J. CUGBP1 is required for IFNbeta-mediated induction of dominant-negative CEBPbeta and suppression of SIV replication in macrophages. J Immunol. 2007;179:7262-9 pubmed
  23. Ejarque Ortiz A, Medina M, Tusell J, Perez Gonzalez A, Serratosa J, Saura J. Upregulation of CCAAT/enhancer binding protein beta in activated astrocytes and microglia. Glia. 2007;55:178-88 pubmed
    ..Given the nature of the C/EBPbeta-regulated genes, we hypothesize that this factor participates in neurotoxic effects associated with glial activation. (c) 2006 Wiley-Liss, Inc. ..
  24. Fox K, Fankell D, Erickson P, Majka S, Crossno J, Klemm D. Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. J Biol Chem. 2006;281:40341-53 pubmed
    ..The data also indicate that CREB not only functions during the initiation of adipogenic conversion but also at later stages. ..
  25. Uematsu S, Kaisho T, Tanaka T, Matsumoto M, Yamakami M, Omori H, et al. The C/EBP beta isoform 34-kDa LAP is responsible for NF-IL-6-mediated gene induction in activated macrophages, but is not essential for intracellular bacteria killing. J Immunol. 2007;179:5378-86 pubmed
    ..Collectively, we demonstrated that 34-kDa LAP is responsible for NF-IL6-mediated gene induction, but not essential for intracellular bacteria killing in activated macrophages. ..
  26. Ranjan P, Boss J. C/EBPbeta regulates TNF induced MnSOD expression and protection against apoptosis. Apoptosis. 2006;11:1837-49 pubmed
    ..These results suggest a role for C/EBPbeta in MnSOD regulation through remodeling of local chromatin structure. ..
  27. Caramel J, Medjkane S, Quignon F, Delattre O. The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors. Oncogene. 2008;27:2035-44 pubmed
  28. Bundy L, Wells S, Sealy L. C/EBPbeta-2 confers EGF-independent growth and disrupts the normal acinar architecture of human mammary epithelial cells. Mol Cancer. 2005;4:43 pubmed
  29. Zhao X, Zhuang S, Chen Y, Boss G, Pilz R. Cyclic GMP-dependent protein kinase regulates CCAAT enhancer-binding protein beta functions through inhibition of glycogen synthase kinase-3. J Biol Chem. 2005;280:32683-92 pubmed
    ..We conclude that cGMP increases the DNA binding potential of C/EBPbeta by preventing the negative effects of GSK-3 phosphorylation. ..
  30. Birsoy K, Chen Z, Friedman J. Transcriptional regulation of adipogenesis by KLF4. Cell Metab. 2008;7:339-47 pubmed publisher
    ..KLF4 is specifically induced in response to cAMP, which by itself can partially activate adipogenesis. These data suggest that KLF4 functions as an immediate early regulator of adipogenesis to induce C/EBPbeta. ..
  31. CESENA T, Cui T, Subramanian L, Fulton C, INIGUEZ LLUHI J, Kwok R, et al. Acetylation and deacetylation regulate CCAAT/enhancer binding protein beta at K39 in mediating gene transcription. Mol Cell Endocrinol. 2008;289:94-101 pubmed publisher
    ..These findings suggest that acetylation of C/EBPbeta at K39 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function. ..
  32. Wang H, Peiris T, Mowery A, Le Lay J, Gao Y, Greenbaum L. CCAAT/enhancer binding protein-beta is a transcriptional regulator of peroxisome-proliferator-activated receptor-gamma coactivator-1alpha in the regenerating liver. Mol Endocrinol. 2008;22:1596-605 pubmed publisher
    ..The demonstration of a functional link between C/EBPbeta and PGC-1alpha activation provides a likely mechanism for how upstream signaling pathways in the regenerating liver can enable the adaptation to the changed metabolic status. ..
  33. Yang W, Molenaar A, Kurts Ebert B, Seyfert H. NF-kappaB factors are essential, but not the switch, for pathogen-related induction of the bovine beta-defensin 5-encoding gene in mammary epithelial cells. Mol Immunol. 2006;43:210-25 pubmed
    ..Our data suggest that elevated levels of binding competent NF-kappaB factors mediated via TLR pathogen recognitions mechanisms are not the key switch for pathogen related induction of the BNBD5-encoding gene in MEC. ..
  34. Zanotti S, Stadmeyer L, Smerdel Ramoya A, Durant D, Canalis E. Misexpression of CCAAT/enhancer binding protein beta causes osteopenia. J Endocrinol. 2009;201:263-74 pubmed publisher
    ..In conclusion, C/EBP beta plays a role in mesenchymal cell differentiation and its misexpression in vivo causes osteopenia. ..
  35. Bagchi M, Mantena S, Kannan A, Bagchi I. Control of uterine cell proliferation and differentiation by C/EBPbeta: functional implications for establishment of early pregnancy. Cell Cycle. 2006;5:922-5 pubmed
    ..It is postulated that C/EBPbeta controls the expression of critical molecules that regulate proliferation and function of epithelial and stromal cells in the female reproductive tract during the establishment of early pregnancy. ..
  36. Kapadia R, Tureyen K, Bowen K, Kalluri H, Johnson P, Vemuganti R. Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein beta knockout mice following transient focal cerebral ischemia. J Neurochem. 2006;98:1718-31 pubmed
    ..These results suggest a significant role for C/EBPbeta in postischemic inflammation and brain damage. ..
  37. Villagra A, Cruzat F, Carvallo L, Paredes R, Olate J, Van Wijnen A, et al. Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity. J Biol Chem. 2006;281:22695-706 pubmed
    ..Together, our results indicate that the SWI/SNF complex is a key regulator of the chromatin-remodeling events that promote tissue-specific transcription in osteoblasts. ..
  38. Jundt F, Raetzel N, Muller C, Calkhoven C, Kley K, Mathas S, et al. A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood. 2005;106:1801-7 pubmed
    ..RAD down-regulated the truncated isoform of the transcription factor CCAAT enhancer binding protein beta (C/EBPbeta), which is known to disrupt terminal differentiation and induce a transformed phenotype...
  39. Harrison J, Huang Y, Wilson K, Kelly P, Adams D, Gronowicz G, et al. Col1a1 promoter-targeted expression of p20 CCAAT enhancer-binding protein beta (C/EBPbeta), a truncated C/EBPbeta isoform, causes osteopenia in transgenic mice. J Biol Chem. 2005;280:8117-24 pubmed
    ..3-green fluorescent protein, demonstrating a cell-autonomous effect of the transgene. These data suggested that C/EBP transcription factors may be important determinants of osteoblast function and bone mass. ..
  40. 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. ..
  41. Luedde T, Duderstadt M, Streetz K, Tacke F, Kubicka S, Manns M, et al. C/EBP beta isoforms LIP and LAP modulate progression of the cell cycle in the regenerating mouse liver. Hepatology. 2004;40:356-65 pubmed
    ..In the context of previous studies, our results demonstrate that LAP, through a dose-dependent effect, withholds a dual activating and inhibiting role on hepatocyte proliferation in vivo. ..
  42. Shuman J, Sebastian T, Kaldis P, Copeland T, Zhu S, Smart R, et al. Cell cycle-dependent phosphorylation of C/EBPbeta mediates oncogenic cooperativity between C/EBPbeta and H-RasV12. Mol Cell Biol. 2004;24:7380-91 pubmed
  43. Pomerance M, Mockey M, Young J, Quillard J, Blondeau J. Expression, hormonal regulation, and subcellular localization of CCAAT/enhancer-binding protein-beta in rat and human thyrocytes. Thyroid. 2005;15:197-204 pubmed
    ..These data suggest that this factor may play important roles in the regulation of thyroidspecific genes and processes, and that its functions are altered in human thyroid carcinoma. ..
  44. Nadeau S, Hein P, Fernandes K, Peterson A, Miller F. A transcriptional role for C/EBP beta in the neuronal response to axonal injury. Mol Cell Neurosci. 2005;29:525-35 pubmed
    ..Thus, C/EBPbeta is essential for the neuronal injury response, acting to transcriptionally activate regeneration-associated gene expression...
  45. Chang W, Rewari A, Centrella M, McCarthy T. Fos-related antigen 2 controls protein kinase A-induced CCAAT/enhancer-binding protein beta expression in osteoblasts. J Biol Chem. 2004;279:42438-44 pubmed
  46. Hata K, Nishimura R, Ueda M, Ikeda F, Matsubara T, Ichida F, et al. A CCAAT/enhancer binding protein beta isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes. Mol Cell Biol. 2005;25:1971-9 pubmed
    ..Thus, identification of a novel role of the C/EBPbeta isoform provides insight into the molecular basis of the regulation of osteoblast and adipocyte commitment. ..
  47. Cieslik K, Zhu Y, Shtivelband M, Wu K. Inhibition of p90 ribosomal S6 kinase-mediated CCAAT/enhancer-binding protein beta activation and cyclooxygenase-2 expression by salicylate. J Biol Chem. 2005;280:18411-7 pubmed
    ..We conclude that salicylate inhibits C/EBPbeta-mediated COX-2 transcriptional activation by blocking RSK activity and Ras signaling pathway. ..
  48. Jana M, Anderson J, Saha R, Liu X, Pahan K. Regulation of inducible nitric oxide synthase in proinflammatory cytokine-stimulated human primary astrocytes. Free Radic Biol Med. 2005;38:655-64 pubmed
    ..However, the activation of NF-kappaB and C/EBPbeta was involved in the induction of iNOS by IL-1beta as well as by IL-IF. ..
  49. Carmona M, Hondares E, Rodriguez de la Concepción M, Rodríguez Sureda V, Peinado Onsurbe J, Poli V, et al. Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPbeta. Biochem J. 2005;389:47-56 pubmed
    ..In summary, defective thermoregulation owing to the lack of C/EBPbeta is associated with the reduced capacity to supply fatty acids as fuels to sustain brown fat thermogenesis. ..
  50. Rochford J, Semple R, Laudes M, Boyle K, Christodoulides C, Mulligan C, et al. ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesis. Mol Cell Biol. 2004;24:9863-72 pubmed
    ..These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis. ..
  51. Rosen E. The transcriptional basis of adipocyte development. Prostaglandins Leukot Essent Fatty Acids. 2005;73:31-4 pubmed
    ..These approaches will be discussed, along with the roles of some new transcriptional players in adipogenesis, including the O/E family of proteins. ..
  52. Friedman J, Larris B, Le P, Peiris T, Arsenlis A, Schug J, et al. Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation. Proc Natl Acad Sci U S A. 2004;101:12986-91 pubmed
    ..This approach is generally applicable to the discovery of direct, biologically relevant targets of mammalian transcription factors. ..
  53. Feng R, Desbordes S, Xie H, Tillo E, Pixley F, Stanley E, et al. PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells. Proc Natl Acad Sci U S A. 2008;105:6057-62 pubmed publisher
    ..Our data suggest that it might become possible to induce the transdifferentiation of skin-derived fibroblasts into cell types desirable for tissue regeneration. ..