Gene transcriptions/Boxes/AP-1 A and Bs

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Although "macrophage proliferation and activation induce MKP-1 with different kinetics, gene expression is mediated by the proximal promoter sequences localized between -380 and -180bp. Mutagenesis experiments of the proximal element determined that CRE/AP-1 is required for LPS- or M-CSF-induced activation of the MKP-1 gene. Moreover, the results from gel shift analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to the CRE/AP-1 box."[1]

The "same region, which contains a CREB/AP-1 box, is required for M-CSF- or LPS-dependent stimulation, although this stimulation is induced at different times after stimulation. [...] CREB and c-Jun are responsible for MKP-1 induction. The induction of c-Jun is correlated with the kinetics of MKP-1 induction by M-CSF or LPS."[1]

"MKP-1 expression induced by M-CSF or LPS is regulated by a CREB/AP-1 box."[1]

The "CRE/AP-1 box (TGACGTCT), which has been reported to be involved in the regulation of several genes [43], was critical."[1]

"When we mutated either the CRE or the AP-1 box, M-CSF- or LPS- dependent inducibility was lost [...]. Surprisingly, although the kinetics of inductions differed, the same region controlled M-CSF- and LPS-stimulated MKP-1 expression."[1]

"The DNA fragment spanned the promoter region from -193 to -169 bp containing the CRE/AP-1 box."[1]

"AP-1 is not a single protein but a series of dimeric basic region-leucine zipper proteins that belong to the Jun (c-Jun, JunB, JunD), Fos (c-Fos, FosB, Fra-1 and Fra2), and ATF (ATF2, LRF1/ATF3, B-ATF, JDP1, JDP2) subfamilies, which recognize either 12-otetradecanoylphorbol-13-acetate response elements (5'-TGAG/CTCA-3') or cAMP response elements (CRE, 5'-TGACGTCA-3') [44]."[1]

GeneID: 2353 FOS Fos proto-oncogene, AP-1 transcription factor subunit. Also known as p55; AP-1; C-FOS. "The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. In some cases, expression of the FOS gene has also been associated with apoptotic cell death."[2]

"The DNA fragment spanned the promoter region from -193 to -169 bp containing the CRE/AP-1 box."[1]

"The human [Transforming growth factor b1] TGFB1 promoter region contains two binding sequences for [Activator protein-1] AP-1, designated AP-1 box A (TGACTCT) and box B (TGTCTCA), which mediate the upregulation of promoter activity via a PKC-dependent pathway after exposure of cells to a high-glucose environment (Refs 37, 38)."[3]

"Several transcription factors have been implicated in glucose-mediated expression of genes involved in diabetic nephropathy. This review focuses on the transcription factors upstream stimulatory factors 1 and 2 (USF1 and 2), activator protein 1 (AP-1), nuclear factor (NF)-κB, cAMP-response-element-binding protein (CREB), nuclear factor of activated T cells (NFAT), and stimulating protein 1 (Sp1). In response to high glucose, several of these transcription factors regulate the gene encoding the profibrotic cytokine transforming growth factor β, as well as genes for a range of other proteins implicated in inflammation and extracellular matrix turnover, including thrombospondin 1, the chemokine CCL2, osteopontin, fibronectin, decorin, plasminogen activator inhibitor 1 and aldose reductase."[3]

DNA-binding domains[edit | edit source]

There are approximately 2600 proteins in the human genome that contain DNA-binding domains, and most of these are presumed to function as transcription factors,[4] though other studies indicate it to be a smaller number.[5] Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors). Hence, the combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development.[6]

A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a general affinity to DNA.[7]

Examples of specific transcription factor DBDs[8]
Factor Structural type Recognition sequence Consensus sequence Binds as
Sp1 transcription factor (SP1) Zinc finger 5'-GGGCGG-3' 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' Monomer
AP-1 transcription factor (AP-1) Basic zipper 5'-TGA(G/C)TCA-3' 5'-TGA G/C TCA-3'.[9] Dimer
Ccaat-enhancer-binding proteins (C/EBP) Basic zipper 5'-ATTGCGCAAT-3' CCAAT box Dimer
Heat shock factor Basic zipper 5'-XGAAX-3' three oppositely oriented "AGAAN" motifs or a degenerate version thereof Trimer
ATF/CREB Basic zipper 5'-TGACGTCA-3' CRE box Dimer
c-Myc Basic helix-loop-helix 5'-CACGTG-3' E-box (Enhancer Box) Dimer
POU2F1 (Oct-1) Helix-turn-helix 5'-ATGCAAAT-3' 5'-ATGCAAAT-3' Monomer
Nuclear factor 1 (NF-1) Novel 5'-TTGGCXXXXXGCCAA-3' 5'-TTGGCXXXXXGCCAA-3' Dimer
(G/C) = G or C
X = A, T, G or C

See also[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Cristina Casals‐Casas, Eva Álvarez, Maria Serra, Carolina de la Torre, Consol Farrera, Ester Sánchez‐Tilló, Carme Caelles, Jorge Lloberas, and Antonio Celada (7 July 2009). "CREB and AP-1 activation regulates MKP-1 induction by LPS or M-CSF and their kinetics correlate with macrophage activation versus proliferation". European Journal Immunology 39 (7): 1902-1913. doi:10.1002/eji.200839037. Retrieved 16 September 2018. 
  2. RefSeq (July 2008). Fos proto-oncogene, AP-1 transcription factor subunit. Bethesda, MD, USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 12 September 2018.
  3. 3.0 3.1 Amber Paratore Sanchez and Kumar Sharma (July 2009). "Transcription factors in the pathogenesis of diabetic nephropathy". Expert Reviews in Molecular Medicine 11: e13. doi:10.1017/S1462399409001057. Retrieved 1 October 2018. 
  4. Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA (2004). "Structure and evolution of transcriptional regulatory networks". Curr. Opin. Struct. Biol. 14 (3): 283–91. doi:10.1016/ PMID 15193307. 
  6. Brivanlou AH, Darnell JE (2002). "Signal transduction and the control of gene expression". Science 295 (5556): 813–8. doi:10.1126/science.1066355. PMID 11823631. 
  7. Lilley, David M. J. (1995). DNA-protein: structural interactions. Oxford: IRL Press at Oxford University Press. ISBN 0-19-963453-X.
  8. Walter F. Boron (2003). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. pp. 125–126. ISBN 1-4160-2328-3.
  9. Angel, P; Imagawa, M; Chiu, R; Stein, B; Imbra, RJ; Rahmsdorf, HJ; Jonat, C; Herrlich, P et al. (19 June 1987). "Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.". Cell 49 (6): 729–39. doi:10.1016/0092-8674(87)90611-8. PMID 3034432. 

External links[edit | edit source]