AP-1 transcription factor

Last updated
Crystal structure of c-Fos:c-Jun heterodimer and DNA complex (PDB: 1FOS ). In the "Leucine zipper" domain (gray), the hydrophobic residues on c-Fos and hydrophobic residues on c-Jun pack together on the interface of the coiled-coil (leucines are colored in blue, and the other hydrophobic residues are colored in yellow). Residues from the "basic region" (purple) directly interact with the DNA (red). UM chem505 1FOS c-jun , c-fos heterodimer.png
Crystal structure of c-Fos:c-Jun heterodimer and DNA complex ( PDB: 1FOS ​). In the "Leucine zipper" domain (gray), the hydrophobic residues on c-Fos and hydrophobic residues on c-Jun pack together on the interface of the coiled-coil (leucines are colored in blue, and the other hydrophobic residues are colored in yellow). Residues from the "basic region" (purple) directly interact with the DNA (red).
AP-1 Proteins (Fos, ATF, JDP)
Identifiers
SymbolAP-1
InterPro IPR000837
Transcription factor Jun
Identifiers
SymbolLeuzip_Jun
InterPro IPR002112

Activator protein 1 (AP-1) is a transcription factor that regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. [1] AP-1 controls a number of cellular processes including differentiation, proliferation, and apoptosis. [2] The structure of AP-1 is a heterodimer composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families.

Contents

History

AP-1 was first discovered as a TPA-activated transcription factor that bound to a cis-regulatory element of the human metallothionein IIa (hMTIIa) promoter and SV40. [3] The AP-1 binding site was identified as the 12-O-Tetradecanoylphorbol-13-acetate (TPA) response element (TRE) with the consensus sequence 5’-TGA G/C TCA-3’. [4] The AP-1 subunit Jun was identified as a novel oncoprotein of avian sarcoma virus, and Fos-associated p39 protein was identified as the transcript of the cellular Jun gene. Fos was first isolated as the cellular homologue of two viral v-fos oncogenes, both of which induce osteosarcoma in mice and rats. [5] Since its discovery, AP-1 has been found to be associated with numerous regulatory and physiological processes, and new relationships are still being investigated.

Structure

UM chem505 group 7 1JUN helical wheel.jpg
UM chem505 1JUN side view.png
C-JUN homodimer ( PDB: 1JUN ​) Left: The helical wheel projection of c-jun homodimer. When viewed down the axis, the alpha helices have a ~7 amino acid repeating leucine at position a. Two helices may be aligned so that repeating hydrophobic side chains (gray) form an interacting surface which facilitates dimerization. Dashed lines indicate potential electrostatic bridges. Right: Side view of c-jun homodimer. Residues on position a and d in helical wheel diagram are shown. Leucines are colored in blue, and other hydrophobic residues are colored in yellow.

AP-1 transcription factor is assembled through the dimerization of a characteristic bZIP domain (basic region leucine zipper) in the Fos and Jun subunits. A typical bZIP domain consists of a “leucine zipper” region, and a “basic region”. The leucine zipper is responsible for dimerization of the Jun and Fos protein subunits. This structural motif twists two alpha helical protein domains into a “coiled coil,” characterized by a periodicity of 3.5 residues per turn and repetitive leucines appearing at every seventh position of the polypeptide chain. Due to the amino acid sequence and the periodicity of the helices, the leucine side chains are arranged along one face of the α helix and form a hydrophobic surface that modulates dimerization. [6] Hydrophobic residues additional to leucine also form the characteristic 3-4 repeat of α helices involved in “coiled-coil” interactions, and help contribute to the hydrophobic packing that drives dimerization. Together, this hydrophobic surface holds the two subunits together. [7] [8]

The basic region of the bZIP domain is just upstream to the leucine zipper, and contains positively charged residues. This region interacts with DNA target sites. [9] Apart from the “leucine zipper” and the “basic region” which are important for dimerization and DNA-binding, the c-jun protein contains three short regions, which consist of clusters of negatively charged amino acids in its N-terminal half that are important for transcriptional activation in vivo. [10]

Dimerization happens between the products of the c-jun and c-fos protooncogenes, and is required for DNA-binding. Jun proteins can form both homo and heterodimers and therefore are capable of binding to DNA by themselves. However, Fos proteins do not dimerize with each other and therefore can only bind to DNA when bound with Jun. [11] [12] The Jun-Fos heterodimer is more stable and has higher DNA-binding activity than Jun homodimers.

Function

AP-1 transcription factor has been shown to have a hand in a wide range of cellular processes, including cell growth, differentiation, and apoptosis. AP-1 activity is often regulated via post-translational modifications, DNA binding dimer composition, and interaction with various binding partners. AP-1 transcription factors are also associated with numerous physiological functions especially in determination of organisms’ life span and tissue regeneration. Below are some of the other important functions and biological roles AP-1 transcription factors have been shown to be involved in.

Cell growth, proliferation and senescence

The AP-1 transcription factor has been shown to play numerous roles in cell growth and proliferation. In particular, c-Fos and c-Jun seem to be major players in these processes. C-jun has been shown to be essential for fibroblast proliferation, [13] and levels of both AP-1 subunits have been shown to be expressed above basal levels during cell division. [14] C-fos has also been shown to increase in expression in response to the introduction of growth factors in the cell, further supporting its suggested involvement in the cell cycle. The growth factors TGF alpha, TGF beta, and IL2 have all been shown to stimulate c-Fos, and thereby stimulate cellular proliferation via AP-1 activation. [10]

Cellular senescence has been identified as "a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1", which "defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells". [15] [16]

Cellular differentiation

AP-1 transcription is deeply involved in the modulation of gene expression. Changes in cellular gene expression in the initiation of DNA synthesis and the formation of differentiated derivatives can lead to cellular differentiation. [10] AP-1 has been shown to be involved in cell differentiation in several systems. For example, by forming stable heterodimers with c-Jun, the bZIP region of c-Fos increases the binding of c-Jun to target genes whose activation is involved in the differentiation of chicken embryo fibroblasts (CEF). [17] It has also been shown to participate in endoderm specification. [18]

Apoptosis

AP-1 transcription factor is associated with a broad range of apoptosis related interactions. AP-1 activity is induced by numerous extracellular matrix and genotoxic agents, suggesting involvement in programmed cell death. [2] Many of these stimuli activate the c-Jun N-terminal kinases (JNKs) leading to the phosphorylation of Jun proteins and enhanced transcriptional activity of AP-1 dependent genes. [2] Increases in the levels of Jun and Fos proteins and JNK activity have been reported in scenarios in which cells undergo apoptosis. For example, inactivated c-Jun-ER cells show a normal morphology, while c-Jun-ER activated cells have been shown to be apoptotic. [19]

Regulation of AP-1

Increased AP-1 levels lead to increased transactivation of target gene expression. Regulation of AP-1 activity is therefore critical for cell function and occurs through specific interactions controlled by dimer-composition, transcriptional and post-translational events, and interaction with accessory proteins. [20]

AP-1 functions are heavily dependent on the specific Fos and Jun subunits contributing to AP-1 dimers. [10] The outcome of AP-1 activation is dependent on the complex combinatorial patterns of AP-1 component dimers. [2] The AP-1 complex binds to a palindromic DNA motif (5’-TGA G/C TCA-3’) to regulate gene expression, but specificity is dependent on the dimer composition of the bZIP subunit. [2]

Physiological relevance

AP-1 transcription factor has been shown to be involved in skin physiology, specifically in tissue regeneration. The process of skin metabolism is initiated by signals that trigger undifferentiated proliferative cells to undergo cell differentiation. Therefore, activity of AP-1 subunits in response to extracellular signals may be modified under conditions where the balance of keratinocyte proliferation and differentiation has to be rapidly and temporally altered. [21] The AP-1 transcription factor also has been shown to be involved in breast cancer cell growth through multiple mechanisms, including regulation of cyclin D1, E2F factors and their target genes. c-Jun, which is one of the AP-1 subunits, regulates the growth of breast cancer cells. Activated c-Jun is predominantly expressed at the invasive front in breast cancer and is associated with proliferation of breast cells. [22] Due to the AP-1 regulatory functions in cancer cells, AP-1 modulation is studied as a potential strategy for cancer prevention and therapy. [23] [24] [25]

Regulome

See also

Related Research Articles

<span class="mw-page-title-main">CREB</span> Class of proteins

CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.

<span class="mw-page-title-main">Leucine zipper</span> DNA-binding structural motif

A leucine zipper is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amino acid segment and the display of these amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The polypeptide segments containing these periodic arrays of leucine residues were proposed to exist in an alpha-helical conformation and the leucine side chains from one alpha helix interdigitate with those from the alpha helix of a second polypeptide, facilitating dimerization.

<span class="mw-page-title-main">Protein c-Fos</span> Mammalian protein found in Homo sapiens

Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the FOS gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV. It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun, resulting in the formation of AP-1 complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.

<span class="mw-page-title-main">Transcription factor Jun</span> Mammalian protein found in Homo sapiens

Transcription factor Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun. The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ju-nana, the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.

<span class="mw-page-title-main">Jun dimerization protein</span> Protein-coding gene in the species Homo sapiens

Jun dimerization protein 2 (JUNDM2) is a protein that in humans is encoded by the JDP2 gene. The Jun dimerization protein is a member of the AP-1 family of transcription factors.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.

<span class="mw-page-title-main">JUNB</span> Protein-coding gene in the species Homo sapiens

Transcription factor jun-B is a protein that, in humans, is encoded by the JUNB gene. Transcription factor jun-B is a transcription factor involved in regulating gene activity following the primary growth factor response. It binds to the DNA sequence 5'-TGA[CG]TCA-3'.

<span class="mw-page-title-main">ATF1</span> Protein-coding gene in humans

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

<span class="mw-page-title-main">ATF4</span> Mammalian protein found in Homo sapiens

Activating transcription factor 4 , also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.

<span class="mw-page-title-main">Activating transcription factor 2</span> Protein-coding gene in the species Homo sapiens

Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene.

<span class="mw-page-title-main">DNA damage-inducible transcript 3</span> Human protein and coding gene

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis and has an important role in the cell's stress response.

<span class="mw-page-title-main">USF1</span> Protein-coding gene in the species Homo sapiens

Upstream stimulatory factor 1 is a protein that in humans is encoded by the USF1 gene.

<span class="mw-page-title-main">FOSL1</span> Protein-coding gene in the species Homo sapiens

Fos-related antigen 1 (FRA1) is a protein that in humans is encoded by the FOSL1 gene.

<span class="mw-page-title-main">ZAK</span> Protein-coding gene in the species Homo sapiens

Sterile alpha motif and leucine zipper containing kinase AZK, also known as ZAK, is a human gene.

<span class="mw-page-title-main">MAFG</span> Protein-coding gene in the species Homo sapiens

Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.

<span class="mw-page-title-main">NFE2L1</span> Protein-coding gene in the species Homo sapiens

Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene. Since NFE2L1 is referred to as Nrf1, it is often confused with nuclear respiratory factor 1 (Nrf1).

<span class="mw-page-title-main">FOSL2</span> Protein-coding gene in the species Homo sapiens

Fos-related antigen 2 (FRA2) is a protein that in humans is encoded by the FOSL2 gene.

<span class="mw-page-title-main">MAFK</span> Protein-coding gene in the species Homo sapiens

Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.

<i>BATF</i> (gene) Protein-coding gene in the species Homo sapiens

Basic leucine zipper transcription factor, ATF-like, also known as BATF, is a protein which in humans is encoded by the BATF gene.

bZIP domain Protein domain

The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors.

References

  1. ↑ Hess J, Angel P, Schorpp-Kistner M (December 2004). "AP-1 subunits: quarrel and harmony among siblings". Journal of Cell Science. 117 (Pt 25): 5965–73. doi: 10.1242/jcs.01589 . PMID   15564374.
  2. 1 2 3 4 5 Ameyar M, Wisniewska M, Weitzman JB (August 2003). "A role for AP-1 in apoptosis: the case for and against". Biochimie. 85 (8): 747–52. doi:10.1016/j.biochi.2003.09.006. PMID   14585541.
  3. ↑ Lee W, Haslinger A, Karin M, Tjian R (January 1987). "Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40". Nature. 325 (6102): 368–72. Bibcode:1987Natur.325..368L. doi:10.1038/325368a0. PMID   3027570. S2CID   4314423.
  4. ↑ Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (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. S2CID   23154076.
  5. ↑ Wagner EF (April 2001). "AP-1--Introductory remarks". Oncogene. 20 (19): 2334–5. doi: 10.1038/sj.onc.1204416 . PMID   11402330.
  6. ↑ Landschulz WH, Johnson PF, McKnight SL (June 1988). "The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins". Science. 240 (4860): 1759–64. Bibcode:1988Sci...240.1759L. doi:10.1126/science.3289117. PMID   3289117.
  7. ↑ O'Shea EK, Rutkowski R, Kim PS (January 1989). "Evidence that the leucine zipper is a coiled coil". Science. 243 (4890): 538–42. Bibcode:1989Sci...243..538O. doi:10.1126/science.2911757. PMID   2911757.
  8. ↑ O'Shea EK, Rutkowski R, Stafford WF, Kim PS (August 1989). "Preferential heterodimer formation by isolated leucine zippers from fos and jun". Science. 245 (4918): 646–8. Bibcode:1989Sci...245..646O. doi:10.1126/science.2503872. PMID   2503872.
  9. ↑ Vogt PK, Bos TJ (1990). "jun: oncogene and transcription factor". Advances in Cancer Research. 55: 1–35. doi:10.1016/s0065-230x(08)60466-2. ISBN   9780120066551. PMID   2166997.
  10. 1 2 3 4 Angel P, Karin M (December 1991). "The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1072 (2–3): 129–57. doi:10.1016/0304-419X(91)90011-9. PMID   1751545.
  11. ↑ Kouzarides T, Ziff E (December 1988). "The role of the leucine zipper in the fos-jun interaction". Nature. 336 (6200): 646–51. Bibcode:1988Natur.336..646K. doi:10.1038/336646a0. PMID   2974122. S2CID   4355663.
  12. ↑ Nakabeppu Y, Ryder K, Nathans D (December 1988). "DNA binding activities of three murine Jun proteins: stimulation by Fos". Cell. 55 (5): 907–15. doi:10.1016/0092-8674(88)90146-8. PMID   3142691. S2CID   11057487.
  13. ↑ Karin M, Liu Z, Zandi E (April 1997). "AP-1 function and regulation". Current Opinion in Cell Biology. 9 (2): 240–6. doi:10.1016/S0955-0674(97)80068-3. PMID   9069263.
  14. ↑ Yamashita J, McCauley LK (2006). "The Activating Protein-1 Transcriptional Complex: Essential and Multifaceted Roles in Bone". Clinical Reviews in Bone and Mineral Metabolism. 4 (2): 107–122. doi:10.1385/BMM:4:2:107. S2CID   90318354.
  15. ↑ Zumerle S, Alimonti A (2020). "In and out from senescence". Nat Cell Biol. 22 (7): 753–754. doi: 10.1038/s41556-020-0540-x . PMID   32591745. S2CID   220071911.
  16. ↑ Martínez-Zamudio R, Roux P, de Freitas J, et al. (2020). "AP-1 imprints a reversible transcriptional programme of senescent cells". Nat Cell Biol. 22 (7): 842–855. doi:10.1038/s41556-020-0529-5. PMC   7899185 . PMID   32514071. S2CID   219543898.
  17. ↑ Shaulian E, Karin M (May 2002). "AP-1 as a regulator of cell life and death". Nature Cell Biology. 4 (5): E131–6. doi:10.1038/ncb0502-e131. PMID   11988758. S2CID   34337538.
  18. ↑ Madrigal P, Deng S, Feng Y, Militi S, Goh KJ, Nibhani R, Grandy R, Osnato A, Ortmann D, Brown S, Pauklin S (January 25, 2023). "Epigenetic and transcriptional regulations prime cell fate before division during human pluripotent stem cell differentiation" (PDF). Nature Communications. 14 (405): 405. Bibcode:2023NatCo..14..405M. doi:10.1038/s41467-023-36116-9. PMC   9876972 . PMID   36697417.
  19. ↑ Bossy-Wetzel E, Bakiri L, Yaniv M (April 1997). "Induction of apoptosis by the transcription factor c-Jun". The EMBO Journal. 16 (7): 1695–709. doi:10.1093/emboj/16.7.1695. PMC   1169773 . PMID   9130714.
  20. ↑ Vesely PW, Staber PB, Hoefler G, Kenner L (July 2009). "Translational regulation mechanisms of AP-1 proteins". Mutation Research. 682 (1): 7–12. Bibcode:2009MRRMR.682....7V. doi:10.1016/j.mrrev.2009.01.001. PMID   19167516.
  21. ↑ Angel P, Szabowski A, Schorpp-Kistner M (April 2001). "Function and regulation of AP-1 subunits in skin physiology and pathology". Oncogene. 20 (19): 2413–23. doi: 10.1038/sj.onc.1204380 . PMID   11402337.
  22. ↑ Shen Q, Uray IP, Li Y, Krisko TI, Strecker TE, Kim HT, Brown PH (January 2008). "The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors". Oncogene. 27 (3): 366–77. doi: 10.1038/sj.onc.1210643 . PMID   17637753.
  23. ↑ Eferl R, Wagner EF (November 2003). "AP-1: a double-edged sword in tumorigenesis". Nature Reviews. Cancer. 3 (11): 859–68. doi:10.1038/nrc1209. PMID   14668816. S2CID   35328722.
  24. ↑ Tewari D, Nabavi SF, Nabavi SM, Sureda A, Farooqi AA, Atanasov AG, Vacca RA, Sethi G, Bishayee A (February 2018). "Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention". Pharmacological Research. 128: 366–375. doi:10.1016/j.phrs.2017.09.014. PMID   28951297. S2CID   20160666.
  25. ↑ Kamide D, Yamashita T, Araki K, Tomifuji M, Tanaka Y, Tanaka S, Shiozawa S, Shiotani A (May 2016). "Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model". Cancer Science. 107 (5): 666–73. doi:10.1111/cas.12914. PMC   4970834 . PMID   26918517.
  26. ↑ Proffitt J, Crabtree G, Grove M, Daubersies P, Bailleul B, Wright E, Plumb M (January 1995). "An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene". Gene. 152 (2): 173–9. doi:10.1016/0378-1119(94)00701-S. PMID   7835696.
  27. ↑ Rainio EM, Sandholm J, Koskinen PJ (February 2002). "Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase". Journal of Immunology. 168 (4): 1524–7. doi: 10.4049/jimmunol.168.4.1524 . PMID   11823475.
  28. ↑ Sanyal S, Sandstrom DJ, Hoeffer CA, Ramaswami M (April 2002). "AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila". Nature. 416 (6883): 870–4. Bibcode:2002Natur.416..870S. doi:10.1038/416870a. PMID   11976688. S2CID   4329320.
  29. ↑ Hirayama J, Cardone L, Doi M, Sassone-Corsi P (July 2005). "Common pathways in circadian and cell cycle clocks: light-dependent activation of Fos/AP-1 in zebrafish controls CRY-1a and WEE-1". Proceedings of the National Academy of Sciences of the United States of America. 102 (29): 10194–9. Bibcode:2005PNAS..10210194H. doi: 10.1073/pnas.0502610102 . PMC   1177375 . PMID   16000406.
  30. ↑ Wai PY, Mi Z, Gao C, Guo H, Marroquin C, Kuo PC (July 2006). "Ets-1 and runx2 regulate transcription of a metastatic gene, osteopontin, in murine colorectal cancer cells". The Journal of Biological Chemistry. 281 (28): 18973–82. doi: 10.1074/jbc.M511962200 . PMID   16670084.
  31. ↑ Collins-Hicok J, Lin L, Spiro C, Laybourn PJ, Tschumper R, Rapacz B, McMurray CT (May 1994). "Induction of the rat prodynorphin gene through Gs-coupled receptors may involve phosphorylation-dependent derepression and activation". Molecular and Cellular Biology. 14 (5): 2837–48. doi:10.1128/MCB.14.5.2837. PMC   358652 . PMID   8164647.
  32. 1 2 Behren A, Simon C, Schwab RM, Loetzsch E, Brodbeck S, Huber E, Stubenrauch F, Zenner HP, Iftner T (December 2005). "Papillomavirus E2 protein induces expression of the matrix metalloproteinase-9 via the extracellular signal-regulated kinase/activator protein-1 signaling pathway". Cancer Research. 65 (24): 11613–21. doi: 10.1158/0008-5472.CAN-05-2672 . PMID   16357172.
  33. ↑ Hennigan RF, Stambrook PJ (August 2001). "Dominant negative c-jun inhibits activation of the cyclin D1 and cyclin E kinase complexes". Molecular Biology of the Cell. 12 (8): 2352–63. doi: 10.1091/mbc.12.8.2352 . PMC   58599 . PMID   11514621.
  34. ↑ Knöchel S, Schuler-Metz A, Knöchel W (November 2000). "c-Jun (AP-1) activates BMP-4 transcription in Xenopus embryos". Mechanisms of Development. 98 (1–2): 29–36. doi: 10.1016/S0925-4773(00)00448-2 . PMID   11044605. S2CID   18150052.
  35. 1 2 Kidd M, Hinoue T, Eick G, Lye KD, Mane SM, Wen Y, Modlin IM (December 2004). "Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation". Physiological Genomics. 20 (1): 131–42. doi:10.1152/physiolgenomics.00216.2003. PMID   15602048.
  36. ↑ Heim JM, Singh S, Fülle HJ, Gerzer R (January 1992). "Comparison of a cloned ANF-sensitive guanylate cyclase (GC-A) with particulate guanylate cyclase from adrenal cortex". Naunyn-Schmiedeberg's Archives of Pharmacology. 345 (1): 64–70. doi:10.1007/BF00175471. PMID   1347156. S2CID   22605840.
  37. ↑ Kuo YR, Wu WS, Wang FS (April 2007). "Flashlamp pulsed-dye laser suppressed TGF-beta1 expression and proliferation in cultured keloid fibroblasts is mediated by MAPK pathway". Lasers in Surgery and Medicine. 39 (4): 358–64. doi:10.1002/lsm.20489. PMID   17457842. S2CID   25556684.
  38. ↑ Wu J, Bresnick EH (March 2007). "Glucocorticoid and growth factor synergism requirement for Notch4 chromatin domain activation". Molecular and Cellular Biology. 27 (6): 2411–22. doi:10.1128/MCB.02152-06. PMC   1820485 . PMID   17220278.
  39. ↑ Martins G, Calame K (2008). "Regulation and functions of Blimp-1 in T and B lymphocytes". Annual Review of Immunology. 26: 133–69. doi:10.1146/annurev.immunol.26.021607.090241. PMID   18370921.
  40. ↑ Lunec J, Holloway K, Cooke M, Evans M (2003). "Redox-regulation of DNA repair". BioFactors. 17 (1–4): 315–24. doi:10.1002/biof.5520170131. PMID   12897453. S2CID   30654477.
  41. ↑ Manicassamy S, Gupta S, Huang Z, Sun Z (June 2006). "Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up-regulating Bcl-xL". Journal of Immunology. 176 (11): 6709–16. doi: 10.4049/jimmunol.176.11.6709 . PMID   16709830.
  42. ↑ Wang N, Verna L, Hardy S, Forsayeth J, Zhu Y, Stemerman MB (September 1999). "Adenovirus-mediated overexpression of c-Jun and c-Fos induces intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human endothelial cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 19 (9): 2078–84. doi: 10.1161/01.ATV.19.9.2078 . PMID   10479648.
  43. ↑ Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K, Iba H (May 2008). "miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism". Journal of Molecular Biology. 378 (3): 492–504. doi:10.1016/j.jmb.2008.03.015. PMID   18384814.
  44. ↑ von Knethen A, Callsen D, Brüne B (February 1999). "NF-kappaB and AP-1 activation by nitric oxide attenuated apoptotic cell death in RAW 264.7 macrophages". Molecular Biology of the Cell. 10 (2): 361–72. doi:10.1091/mbc.10.2.361. PMC   25174 . PMID   9950682.
  45. ↑ Phelan JP, Millson SH, Parker PJ, Piper PW, Cooke FT (October 2006). "Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiae". Journal of Cell Science. 119 (Pt 20): 4225–34. doi: 10.1242/jcs.03188 . PMID   17003107.
  46. ↑ Nolasco LH, Turner NA, Bernardo A, Tao Z, Cleary TG, Dong JF, Moake JL (December 2005). "Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers". Blood. 106 (13): 4199–209. doi:10.1182/blood-2005-05-2111. PMC   1895236 . PMID   16131569.
  47. ↑ Hommura F, Katabami M, Leaner VD, Donninger H, Sumter TF, Resar LM, Birrer MJ (May 2004). "HMG-I/Y is a c-Jun/activator protein-1 target gene and is necessary for c-Jun-induced anchorage-independent growth in Rat1a cells". Molecular Cancer Research. 2 (5): 305–14. doi: 10.1158/1541-7786.305.2.5 . PMID   15192124. S2CID   25127065.
  48. ↑ Chang CJ, Chao JC (April 2002). "Effect of human milk and epidermal growth factor on growth of human intestinal Caco-2 cells". Journal of Pediatric Gastroenterology and Nutrition. 34 (4): 394–401. doi: 10.1097/00005176-200204000-00015 . PMID   11930096. S2CID   25446228.
  49. ↑ Weber JR, Skene JH (July 1998). "The activity of a highly promiscuous AP-1 element can be confined to neurons by a tissue-selective repressive element". The Journal of Neuroscience. 18 (14): 5264–74. doi: 10.1523/jneurosci.18-14-05264.1998 . PMC   6793474 . PMID   9651209.
  50. ↑ Lee W, Mitchell P, Tjian R (June 1987). "Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements". Cell. 49 (6): 741–52. doi:10.1016/0092-8674(87)90612-X. PMID   3034433. S2CID   37036603.
  51. ↑ Cohen MP, Ziyadeh FN, Lautenslager GT, Cohen JA, Shearman CW (May 1999). "Glycated albumin stimulation of PKC-beta activity is linked to increased collagen IV in mesangial cells". The American Journal of Physiology. 276 (5 Pt 2): F684–90. doi: 10.1152/ajprenal.1999.276.5.F684 . PMID   10330050.
  52. ↑ Stark CJ, Atreya CD (April 2005). "Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies". Virology Journal. 2: 35. doi: 10.1186/1743-422X-2-35 . PMC   1087510 . PMID   15833113.
  53. 1 2 3 Lane SJ, Adcock IM, Richards D, Hawrylowicz C, Barnes PJ, Lee TH (December 1998). "Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes". The Journal of Clinical Investigation. 102 (12): 2156–64. doi:10.1172/JCI2680. PMC   509170 . PMID   9854051.
  54. ↑ Steiner C, Peters WH, Gallagher EP, Magee P, Rowland I, Pool-Zobel BL (March 2007). "Genistein protects human mammary epithelial cells from benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and 4-hydroxy-2-nonenal genotoxicity by modulating the glutathione/glutathione S-transferase system". Carcinogenesis. 28 (3): 738–48. doi: 10.1093/carcin/bgl180 . PMID   17065199.
  55. ↑ Ahn JD, Morishita R, Kaneda Y, Lee KU, Park JY, Jeon YJ, Song HS, Lee IK (June 2001). "Transcription factor decoy for activator protein-1 (AP-1) inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor (PAI-1) gene expression in cultured human vascular smooth muscle cells". Diabetologia. 44 (6): 713–20. doi: 10.1007/s001250051680 . PMID   11440364.
  56. ↑ Kang S, Fisher GJ, Voorhees JJ (November 2001). "Photoaging: pathogenesis, prevention, and treatment". Clinics in Geriatric Medicine. 17 (4): 643–59, v–vi. doi:10.1016/S0749-0690(05)70091-4. PMID   11535421.
  57. ↑ Navasa M, Gordon DA, Hariharan N, Jamil H, Shigenaga JK, Moser A, Fiers W, Pollock A, Grunfeld C, Feingold KR (June 1998). "Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines". Journal of Lipid Research. 39 (6): 1220–30. doi: 10.1016/S0022-2275(20)32546-3 . PMID   9643353.
  58. ↑ Suetsugu M, Takano A, Nagai A, Takeshita A, Hirose K, Matsumoto K, et al. (2007). "Retinoic acid inhibits serum-stimulated activator protein-1 via suppression of c-fos and c-jun gene expressions during the vitamin-induced differentiation of mouse osteoblastic cell line MC3T3-E1 cells" (PDF). J. Meikai Dent. Med. 36 (1): 42–50.
  59. ↑ Inagi R, Miyata T, Nangaku M, Ueyama H, Takeyama K, Kato S, Kurokawa K (November 2002). "Transcriptional regulation of a mesangium-predominant gene, megsin". Journal of the American Society of Nephrology. 13 (11): 2715–22. doi: 10.1097/01.ASN.0000033507.32175.FA . PMID   12397041.
  60. ↑ Kim S, Yu SS, Lee IS, Ohno S, Yim J, Kim S, Kang HS (April 1999). "Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s)". The Journal of General Virology. 80 ( Pt 4) (4): 961–9. doi: 10.1099/0022-1317-80-4-961 . PMID   10211966.
  61. ↑ Masuda A, Yoshikai Y, Kume H, Matsuguchi T (November 2004). "The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells". Journal of Immunology. 173 (9): 5564–73. doi: 10.4049/jimmunol.173.9.5564 . PMID   15494506.
  62. ↑ Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The Journal of Biological Chemistry. 274 (47): 33684–90. doi: 10.1074/jbc.274.47.33684 . PMID   10559258.
  63. ↑ Simantov R (August 1995). "Neurotransporters: regulation, involvement in neurotoxicity, and the usefulness of antisense nucleic acids". Biochemical Pharmacology. 50 (4): 435–42. doi:10.1016/0006-2952(95)00068-B. PMID   7646547.
  64. ↑ Yang HS, Jansen AP, Nair R, Shibahara K, Verma AK, Cmarik JL, Colburn NH (February 2001). "A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation". Oncogene. 20 (6): 669–76. doi: 10.1038/sj.onc.1204137 . PMID   11314000.
  65. ↑ Xie J, Pan H, Yoo S, Gao SJ (December 2005). "Kaposi's sarcoma-associated herpesvirus induction of AP-1 and interleukin 6 during primary infection mediated by multiple mitogen-activated protein kinase pathways". Journal of Virology. 79 (24): 15027–37. doi:10.1128/JVI.79.24.15027-15037.2005. PMC   1316010 . PMID   16306573.
  66. ↑ Khan MA, Bouzari S, Ma C, Rosenberger CM, Bergstrom KS, Gibson DL, Steiner TS, Vallance BA (April 2008). "Flagellin-dependent and -independent inflammatory responses following infection by enteropathogenic Escherichia coli and Citrobacter rodentium". Infection and Immunity. 76 (4): 1410–22. doi:10.1128/IAI.01141-07. PMC   2292885 . PMID   18227166.
  67. ↑ Kida Y, Inoue H, Shimizu T, Kuwano K (January 2007). "Serratia marcescens serralysin induces inflammatory responses through protease-activated receptor 2". Infection and Immunity. 75 (1): 164–74. doi:10.1128/IAI.01239-06. PMC   1828393 . PMID   17043106.
  68. ↑ Gutzman JH, Rugowski DE, Schroeder MD, Watters JJ, Schuler LA (December 2004). "Multiple kinase cascades mediate prolactin signals to activating protein-1 in breast cancer cells". Molecular Endocrinology. 18 (12): 3064–75. doi:10.1210/me.2004-0187. PMC   1634796 . PMID   15319452.
  69. ↑ Brinkmann MM, Glenn M, Rainbow L, Kieser A, Henke-Gendo C, Schulz TF (September 2003). "Activation of mitogen-activated protein kinase and NF-kappaB pathways by a Kaposi's sarcoma-associated herpesvirus K15 membrane protein". Journal of Virology. 77 (17): 9346–58. doi: 10.1128/JVI.77.17.9346-9358.2003 . PMC   187392 . PMID   12915550.
  70. ↑ Greenstein S, Ghias K, Krett NL, Rosen ST (June 2002). "Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies". Clinical Cancer Research. 8 (6): 1681–94. PMID   12060604.
  71. ↑ Yokoo T, Kitamura M (May 1996). "Antioxidant PDTC induces stromelysin expression in mesangial cells via a tyrosine kinase-AP-1 pathway". The American Journal of Physiology. 270 (5 Pt 2): F806–11. doi:10.1152/ajprenal.1996.270.5.F806. PMID   8928842.
  72. ↑ Chang CF, Cho S, Wang J (April 2014). "(-)-Epicatechin protects hemorrhagic brain via synergistic Nrf2 pathways". Annals of Clinical and Translational Neurology. 1 (4): 258–271. doi:10.1002/acn3.54. PMC   3984761 . PMID   24741667.
  73. ↑ Gibbings DJ, Ghetu AF, Dery R, Befus AD (February 2008). "Macrophage migration inhibitory factor has a MHC class I-like motif and function". Scandinavian Journal of Immunology. 67 (2): 121–32. doi: 10.1111/j.1365-3083.2007.02046.x . PMID   18201367.
  74. ↑ Uniprot Database
  75. ↑ Hseu YC, Vudhya Gowrisankar Y, Chen XZ, Yang YC, Yang HL (Feb 2020). "The antiaging activity of ergothioneine in UVA-irradiated human dermal fibroblasts via the inhibition of the AP-1 pathway and the activation of Nrf2-mediated antioxidant genes". Oxid Med Cell Longev. 2020 (2576823): 1–13. doi: 10.1155/2020/2576823 . PMC   7038158 . PMID   32104530.
  76. ↑ Bahrami S, Drabløs F (2016). "Gene regulation in the immediate-early response process". Advances in Biological Regulation. 62: 37–49. doi: 10.1016/j.jbior.2016.05.001 . PMID   27220739.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.