CEBPD explained

CCAAT/enhancer-binding protein delta is a protein that in humans is encoded by the CEBPD gene.^{[1] [2]}

Function

The protein encoded by this intronless gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-alpha. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses, and may be involved in the regulation of genes associated with activation and/or differentiation of macrophages.^[3]

Functions

CEBPD is involved in regulation of apoptosis and cell proliferation. It probably acts as tumor suppressor.^[4]

One study in mice showed that CEBPD prevents development of tubular injury and tubulointerstitial fibrogenesis during the progression of chronic obstructive nephropathy.^[5]

Function of CEBPD gene can be effectively examined by siRNA knockdown based on an independent validation.^[6]

Interactions

CEBPD has been shown to interact with Mothers against decapentaplegic homolog 3.^[7]

See also

• Ccaat-enhancer-binding proteins

Further reading

• Sladek FM, Darnell JE . Mechanisms of liver-specific gene expression . Current Opinion in Genetics & Development . 2 . 2 . 256–259 . April 1992 . 1638120 . 10.1016/S0959-437X(05)80282-5 .
• Kinoshita S, Akira S, Kishimoto T . A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6 . Proceedings of the National Academy of Sciences of the United States of America . 89 . 4 . 1473–1476 . February 1992 . 1741402 . 48473 . 10.1073/pnas.89.4.1473 . free . 1992PNAS...89.1473K .
• Nagulapalli S, Pongubala JM, Atchison ML . Multiple proteins physically interact with PU.1. Transcriptional synergy with NF-IL6 beta (C/EBP delta, CRP3) . Journal of Immunology . 155 . 9 . 4330–4338 . November 1995 . 7594592 . 10.4049/jimmunol.155.9.4330 . free .
• Wood S, Schertzer M, Yaremko ML . Sequence identity locates CEBPD and FGFR1 to mapped human loci within proximal 8p . Cytogenetics and Cell Genetics . 70 . 3–4 . 188–191 . 1995 . 7789168 . 10.1159/000134030 .
• Cleutjens CB, van Eekelen CC, van Dekken H, Smit EM, Hagemeijer A, Wagner MJ, Wells DE, Trapman J . The human C/EBP delta (CRP3/CELF) gene: structure and chromosomal localization . Genomics . 16 . 2 . 520–523 . May 1993 . 8314590 . 10.1006/geno.1993.1220 .
• Chen PL, Riley DJ, Chen Y, Lee WH . Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs . Genes & Development . 10 . 21 . 2794–2804 . November 1996 . 8946919 . 10.1101/gad.10.21.2794 . free .
• Xia C, Cheshire JK, Patel H, Woo P . Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes . The International Journal of Biochemistry & Cell Biology . 29 . 12 . 1525–1539 . December 1997 . 9570146 . 10.1016/S1357-2725(97)00083-6 .
• Zhu Y, Saunders MA, Yeh H, Deng WG, Wu KK . Dynamic regulation of cyclooxygenase-2 promoter activity by isoforms of CCAAT/enhancer-binding proteins . The Journal of Biological Chemistry . 277 . 9 . 6923–6928 . March 2002 . 11741938 . 10.1074/jbc.M108075200 . free .
• Angeloni D, Lee JD, Johnson BE, Teh BT, Dean M, Lerman MI, Sterneck E . C306A single nucleotide polymorphism in the human CEBPD gene that maps at 8p11.1-p11.2 . Molecular and Cellular Probes . 15 . 6 . 395–397 . December 2001 . 11851384 . 10.1006/mcpr.2001.0377 . free . 8215328 . 11382/3170 .
• Gao H, Parkin S, Johnson PF, Schwartz RC . C/EBP gamma has a stimulatory role on the IL-6 and IL-8 promoters . The Journal of Biological Chemistry . 277 . 41 . 38827–38837 . October 2002 . 12177065 . 10.1074/jbc.M206224200 . free .
• Dearth LR, DeWille J . Posttranscriptional and posttranslational regulation of C/EBP delta in G0 growth-arrested mammary epithelial cells . The Journal of Biological Chemistry . 278 . 13 . 11246–11255 . March 2003 . 12554732 . 10.1074/jbc.M207930200 . free .
• Milde-Langosch K, Löning T, Bamberger AM . Expression of the CCAAT/enhancer-binding proteins C/EBPalpha, C/EBPbeta and C/EBPdelta in breast cancer: correlations with clinicopathologic parameters and cell-cycle regulatory proteins . Breast Cancer Research and Treatment . 79 . 2 . 175–185 . May 2003 . 12825852 . 10.1023/A:1023929504884 . 45020949 .
• Kovács KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR . CCAAT/enhancer-binding protein family members recruit the coactivator CREB-binding protein and trigger its phosphorylation . The Journal of Biological Chemistry . 278 . 38 . 36959–36965 . September 2003 . 12857754 . 10.1074/jbc.M303147200 . free .
• Chen YW, Hubal MJ, Hoffman EP, Thompson PD, Clarkson PM . Molecular responses of human muscle to eccentric exercise . Journal of Applied Physiology . 95 . 6 . 2485–2494 . December 2003 . 12937035 . 10.1152/japplphysiol.01161.2002 . 9817319 .
• Li R, Strohmeyer R, Liang Z, Lue LF, Rogers J . CCAAT/enhancer binding protein delta (C/EBPdelta) expression and elevation in Alzheimer's disease . Neurobiology of Aging . 25 . 8 . 991–999 . September 2004 . 15212823 . 10.1016/j.neurobiolaging.2003.10.016 . 54232508 .
• Sivko GS, Sanford DC, Dearth LD, Tang D, DeWille JW . CCAAT/Enhancer binding protein delta (c/EBPdelta) regulation and expression in human mammary epithelial cells: II. Analysis of activating signal transduction pathways, transcriptional, post-transcriptional, and post-translational control . Journal of Cellular Biochemistry . 93 . 4 . 844–856 . November 2004 . 15389878 . 10.1002/jcb.20224 . 31572695 .

Notes and References

1. Cao Z, Umek RM, McKnight SL . Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells . Genes & Development . 5 . 9 . 1538–1552 . September 1991 . 1840554 . 10.1101/gad.5.9.1538 . free .
2. Williams SC, Cantwell CA, Johnson PF . A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro . Genes & Development . 5 . 9 . 1553–1567 . September 1991 . 1884998 . 10.1101/gad.5.9.1553 . free .
3. Web site: Entrez Gene: CEBPD CCAAT/enhancer binding protein (C/EBP), delta.
4. Gery S, Tanosaki S, Hofmann WK, Koppel A, Koeffler HP . C/EBPdelta expression in a BCR-ABL-positive cell line induces growth arrest and myeloid differentiation . Oncogene . 24 . 9 . 1589–1597 . February 2005 . 15674331 . 10.1038/sj.onc.1208393 . 24347537 .
5. Duitman J, Borensztajn KS, Pulskens WP, Leemans JC, Florquin S, Spek CA . CCAAT-enhancer binding protein delta (C/EBPδ) attenuates tubular injury and tubulointerstitial fibrogenesis during chronic obstructive nephropathy . Laboratory Investigation; A Journal of Technical Methods and Pathology . 94 . 1 . 89–97 . January 2014 . 24247561 . 10.1038/labinvest.2013.127 . free .
6. Munkácsy G, Sztupinszki Z, Herman P, Bán B, Pénzváltó Z, Szarvas N, Győrffy B . Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments . Molecular Therapy. Nucleic Acids . 5 . 9 . e366 . September 2016 . 27673562 . 5056990 . 10.1038/mtna.2016.66 .
7. 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 . The Journal of Biological Chemistry . 278 . 11 . 9609–9619 . March 2003 . 12524424 . 10.1074/jbc.M212259200 . free .