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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/18 15:08:25」(JST)

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CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.^[1]^[2]

Function

The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related proteins CEBP-alpha, CEBP-delta, and CEBP-gamma. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the IL-1 response element in the IL-6 gene, as well as to regulatory regions of several acute-phase and cytokine genes. In addition, the encoded protein can bind the promoter and upstream element and stimulate the expression of the collagen type I gene.^[3]

CEBP-beta is critical for normal macrophage functioning, an important immune cell sub-type; mice unable to express CEBP-beta have macrophages that cannot differentiate (specialize) and thus are unable to perform all their biological functions - including macrophage-mediated muscle repair.^[4] Observational work has shown that expression of CEBP-beta in blood leukocytes is positively associated with muscle strength in humans,^[5] emphasizing the importance of the immune system, and particularly macrophages, in the maintenance of muscle function.

Target genes

CEBPB is capable of increasing the expression of several target genes. Among them, some have specific role in the nervous system such as the preprotachykinin gene, giving rise to substance P and neurokinin A^[6] and the choline acetyltransferase responsible for the biosynthesis of the important neurotransmitter acetylcholine.^[7] Other targets include genes coding for cytokines such as IL-6,^[8] IL-4,^[9] IL-5,^[10] and TNF-alpha.^[11] Genes coding for transporter proteins that confer multidrug resistance to the cells have also been found to be activated by CEBPB. Such genes include ABCC2^[12] and ABCB1.^[13]

Interactions

CEBPB has been shown to interact with:

CREB1^[14]
CRSP3^[15]
DNA damage-inducible transcript 3^[16]^[17]
EP300^[18]
Estrogen receptor alpha^[19]^[20]
Glucocorticoid receptor^[19]
HMGA1^[21]
HSF1^[22]
Nucleolar phosphoprotein p130^[23]
RELA^[24]^[25]
Serum response factor^[26]^[27]
SMARCA2^[28]
Sp1 transcription factor^[21]^[29]
TRIM28^[30]^[31]
Zif268.^[32]

References

^ Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (Jul 1992). "Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF)". Genomics 13 (2): 293–300. doi:10.1016/0888-7543(92)90245-N. PMID 1535333.
^ Cao Z, Umek RM, McKnight SL (Oct 1991). "Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells". Genes Dev 5 (9): 1538–52. doi:10.1101/gad.5.9.1538. PMID 1840554.
^ "Entrez Gene: CEBPB CCAAT/enhancer binding protein (C/EBP), beta". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1051.
^ Ruffel, Daniela; Mourkioti, Foteini., Gambardella, Adriana., Kirstetter, Peggy., Lopez, Rodolphe G., Rosenthal, Nadia., Nerlov, Claus. (2009). "A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair.". Proceedings of the National Academy of Sciences of the United States of America 106 (41): 17475–80. doi:10.1073/pnas.0908641106. PMC 2762675. PMID 19805133. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2762675/.
^ Harries, Lorna; Pilling, Luke C., Hernandez, Dena G., Bradley-Smith, Rachel., Henley, William., Singleton, Andrew B., Guralnik, Jack M., Bandinelli, Stefania., Ferrucci, Luigi., Melzer, David. (2011). "CCAAT-Enhancer-Binding Protein-Beta (CEBPB) Expression In-Vivo is Associated with Muscle Strength.". Aging Cell. doi:10.1111/j.1474-9726.2011.00782.x. PMID 22152057. http://www.ncbi.nlm.nih.gov/pubmed/22152057.
^ Kovács KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR (September 2006). "C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones". J. Neurochem. 98 (5): 1390–9. doi:10.1111/j.1471-4159.2006.03957.x. PMID 16771829.
^ Robert I, Sutter A, Quirin-Stricker C (October 2002). "Synergistic activation of the human choline acetyltransferase gene by c-Myb and C/EBPbeta". Brain Res. Mol. Brain Res. 106 (1–2): 124–35. doi:10.1016/S0169-328X(02)00419-9. PMID 12393272.
^ Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H, Kishimoto T (January 1992). "Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6". Blood 79 (2): 460–6. PMID 1730090.
^ Davydov IV, Krammer PH, Li-Weber M (December 1995). "Nuclear factor-IL6 activates the human IL-4 promoter in T cells". J. Immunol. 155 (11): 5273–9. PMID 7594540.
^ van Dijk TB, Baltus B, Raaijmakers JA, Lammers JW, Koenderman L, de Groot RP (September 1999). "A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene". J. Immunol. 163 (5): 2674–80. PMID 10453008.
^ Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J, Vinson C, Di Liberto M, Ramirez F (February 2000). "Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins". Mol. Cell. Biol. 20 (3): 912–8. doi:10.1128/MCB.20.3.912-918.2000. PMC 85208. PMID 10629048. //www.ncbi.nlm.nih.gov/pmc/articles/PMC85208/.
^ Tanaka T, Uchiumi T, Hinoshita E, Inokuchi A, Toh S, Wada M, Takano H, Kohno K, Kuwano M (December 1999). "The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells". Hepatology 30 (6): 1507–12. doi:10.1002/hep.510300617. PMID 10573531.
^ Chen GK, Sale S, Tan T, Ermoian RP, Sikic BI (April 2004). "CCAAT/enhancer-binding protein beta (nuclear factor for interleukin 6) transactivates the human MDR1 gene by interaction with an inverted CCAAT box in human cancer cells". Mol. Pharmacol. 65 (4): 906–16. doi:10.1124/mol.65.4.906. PMID 15044620.
^ Chen, Yongchang; Zhuang Shunhui, Cassenaer Stijn, Casteel Darren E, Gudi Tanima, Boss Gerry R, Pilz Renate B (Jun. 2003). "Synergism between Calcium and Cyclic GMP in Cyclic AMP Response Element-Dependent Transcriptional Regulation Requires Cooperation between CREB and C/EBP-β". Mol. Cell. Biol. 23 (12): 4066–82. doi:10.1128/MCB.23.12.4066-4082.2003. PMC 156132. PMID 12773552. //www.ncbi.nlm.nih.gov/pmc/articles/PMC156132/.
^ Mo, Xianming; Kowenz-Leutz Elisabeth, Xu Hong, Leutz Achim (Jan. 2004). "Ras induces mediator complex exchange on C/EBP beta". Mol. Cell 13 (2): 241–50. doi:10.1016/S1097-2765(03)00521-5. PMID 14759369.
^ Hattori, Takayuki; Ohoka Nobumichi, Hayashi Hidetoshi, Onozaki Kikuo (Apr. 2003). "C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform". FEBS Lett. 541 (1–3): 33–9. doi:10.1016/S0014-5793(03)00283-7. PMID 12706815.
^ Fawcett, T W; Eastman H B, Martindale J L, Holbrook N J (Jun. 1996). "Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress". J. Biol. Chem. 271 (24): 14285–9. doi:10.1074/jbc.271.24.14285. PMID 8662954.
^ Mink, S; Haenig B, Klempnauer K H (Nov. 1997). "Interaction and functional collaboration of p300 and C/EBPbeta". Mol. Cell. Biol. 17 (11): 6609–17. PMC 232514. PMID 9343424. //www.ncbi.nlm.nih.gov/pmc/articles/PMC232514/.
^ ^a ^b Boruk, M; Savory J G, Haché R J (Nov. 1998). "AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor". Mol. Endocrinol. 12 (11): 1749–63. doi:10.1210/me.12.11.1749. PMID 9817600.
^ Stein, B; Yang M X (Sep. 1995). "Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta". Mol. Cell. Biol. 15 (9): 4971–9. PMC 230744. PMID 7651415. //www.ncbi.nlm.nih.gov/pmc/articles/PMC230744/.
^ ^a ^b Foti, Daniela; Iuliano Rodolfo, Chiefari Eusebio, Brunetti Antonio (Apr. 2003). "A Nucleoprotein Complex Containing Sp1, C/EBPβ, and HMGI-Y Controls Human Insulin Receptor Gene Transcription". Mol. Cell. Biol. 23 (8): 2720–32. doi:10.1128/MCB.23.8.2720-2732.2003. PMC 152545. PMID 12665574. //www.ncbi.nlm.nih.gov/pmc/articles/PMC152545/.
^ Xie, Yue; Chen Changmin, Stevenson Mary Ann, Auron Philip E, Calderwood Stuart K (Apr. 2002). "Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6". J. Biol. Chem. 277 (14): 11802–10. doi:10.1074/jbc.M109296200. PMID 11801594.
^ Miau, L H; Chang C J, Shen B J, Tsai W H, Lee S C (Apr. 1998). "Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation". J. Biol. Chem. 273 (17): 10784–91. doi:10.1074/jbc.273.17.10784. PMID 9553145.
^ Weber, Marion; Sydlik Carmen, Quirling Martina, Nothdurfter Caroline, Zwergal Andreas, Heiss Peter, Bell Susanne, Neumeier Dieter, Ziegler-Heitbrock H W Loms, Brand Korbinian (Jun. 2003). "Transcriptional inhibition of interleukin-8 expression in tumor necrosis factor-tolerant cells: evidence for involvement of C/EBP beta". J. Biol. Chem. 278 (26): 23586–93. doi:10.1074/jbc.M211646200. PMID 12707271.
^ Xia, C; Cheshire J K, Patel H, Woo P (Dec. 1997). "Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes". Int. J. Biochem. Cell Biol. 29 (12): 1525–39. doi:10.1016/S1357-2725(97)00083-6. PMID 9570146.
^ Hanlon, M; Sealy L (May. 1999). "Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta". J. Biol. Chem. 274 (20): 14224–8. doi:10.1074/jbc.274.20.14224. PMID 10318842.
^ Sealy, L; Malone D, Pawlak M (Mar. 1997). "Regulation of the cfos serum response element by C/EBPbeta". Mol. Cell. Biol. 17 (3): 1744–55. PMC 231899. PMID 9032301. //www.ncbi.nlm.nih.gov/pmc/articles/PMC231899/.
^ Kowenz-Leutz, E; Leutz A (Nov. 1999). "A C/EBP beta isoform recruits the SWI/SNF complex to activate myeloid genes". Mol. Cell 4 (5): 735–43. doi:10.1016/S1097-2765(00)80384-6. PMID 10619021.
^ Liu, Yi-Wen; Tseng Hui-Ping, Chen Lei-Chin, Chen Ben-Kuen, Chang Wen-Chang (Jul. 2003). "Functional cooperation of simian virus 40 promoter factor 1 and CCAAT/enhancer-binding protein beta and delta in lipopolysaccharide-induced gene activation of IL-10 in mouse macrophages". J. Immunol. 171 (2): 821–8. PMID 12847250.
^ Rooney, J W; Calame K L (Nov. 2001). "TIF1β functions as a coactivator for C/EBPβ and is required for induced differentiation in the myelomonocytic cell line U937". Genes Dev. 15 (22): 3023–38. doi:10.1101/gad.937201. PMC 312827. PMID 11711437. //www.ncbi.nlm.nih.gov/pmc/articles/PMC312827/. (Retracted. If this is intentional, please replace {{Retracted}} with {{Retracted|intentional=yes}}.)
^ Chang, C J; Chen Y L, Lee S C (Oct. 1998). "Coactivator TIF1β Interacts with Transcription Factor C/EBPβ and Glucocorticoid Receptor To Induce α1-Acid Glycoprotein Gene Expression". Mol. Cell. Biol. 18 (10): 5880–7. PMC 109174. PMID 9742105. //www.ncbi.nlm.nih.gov/pmc/articles/PMC109174/.
^ Zhang, Fang; Lin Meihong, Abidi Parveen, Thiel Gerald, Liu Jingwen (Nov. 2003). "Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene". J. Biol. Chem. 278 (45): 44246–54. doi:10.1074/jbc.M305564200. PMID 12947119.

External links

CEBPB+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
FactorBook CEBPB

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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Related Pictures

IL - 6 has a pleiotropic effect TLR-induced Cytokines I: Viral-induced Interleukin-6 and its receptor, key Signal Transducer and Activator of Figure 2 : NF-[kappa]B, chemokine gene GeneCopoeia: IL 6 signaling pathway Of Nf Kb Inhibition Nearly Every Fruit And

★リンクテーブル★

リンク元	「核因子インターロイキン6」「CCAAT-enhancer-binding protein-beta」「nuclear factor interleukin 6」
関連記事	「I」「IL」「N」「NF」

「核因子インターロイキン6」

CCAAT/enhancer binding protein (C/EBP), beta
	; PDB rendering based on 1ci6.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1GTW, 1GU4, 1GU5, 1H88, 1H89, 1H8A, 1HJB, 1IO4, 2E42, 2E43
Identifiers
Symbols	CEBPB; C/EBP-beta; CRP2; IL6DBP; LAP; NF-IL6; TCF5
External IDs	OMIM: 189965 MGI: 88373 HomoloGene: 3807 GeneCards: CEBPB Gene
Gene Ontology
Molecular function	• RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; • DNA binding; • sequence-specific DNA binding transcription factor activity; • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; • protein binding; • transcription factor binding; • glucocorticoid receptor binding; • protein homodimerization activity; • sequence-specific DNA binding; • protein heterodimerization activity;
Cellular component	• nuclear chromatin; • nucleus; • cytoplasm; • nuclear matrix;
Biological process	• embryonic placenta development; • regulation of transcription, DNA-dependent; • transcription from RNA polymerase II promoter; • induction of apoptosis; • acute-phase response; • inflammatory response; • immune response; • neuron differentiation; • response to lipopolysaccharide; • mammary gland epithelial cell proliferation; • response to endoplasmic reticulum stress; • regulation of interleukin-6 biosynthetic process; • positive regulation of osteoblast differentiation; • negative regulation of transcription, DNA-dependent; • brown fat cell differentiation; • mammary gland epithelial cell differentiation; • cellular response to amino acid stimulus;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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