C-Jun

c-Jun ist ein Bestandteil des Transkriptionsfaktors AP-1 und ein Protoonkogen.^[1]

JUN
nach PDB 1A02
Andere Namen	Jun Proto-Oncogene V-Jun Avian Sarcoma Virus 17 Oncogene Homolog P39 Jun Activation Domain Binding Protein
Vorhandene Strukturdaten: 1A02, 1FOS, 1JNM, 1JUN, 1S9K, 1T2K
Eigenschaften des menschlichen Proteins
Masse/Länge Primärstruktur	331 Aminosäuren, 35676 Da
Bezeichner
Externe IDs	GeneCards: JUN OMIM: 165160 UniProt P05412
Vorkommen
Homologie-Familie	Hovergen
Orthologe
	Mensch	Hausmaus
Entrez	3725	16476
UniProt	P05412	P05627
PubMed-Suche	3725	16476

Eigenschaften

c-Jun ist am Zellzyklus und der Apoptose beteiligt. Mutationen im Gen von c-Jun treten bei verschiedenen Tumoren auf. c-Jun war der erste beschriebene onkogene Transkriptionsfaktor.^[2] Das Homolog des c-Jun (englisch cellular Jun) aus Retroviren wird als v-Jun (englisch viral Jun) bezeichnet.^[3]

Interaktionen

c-Jun interagiert mit verschiedenen Proteinen:

• TGIF1^[4]
• Ets Related Gene^[5]
• Retinoblastom-Protein^[6]
• CREBBP^[7]
• ATF2^[8][9][10]
• BRCA1-Cofaktor^[11]
• BRCA1^[12]
• c-Fos^{[13][14][15][16][17][18][19]}
• NFE2L1^[19]
• DDX21^[20]
• NFE2L2^[19]
• TATA-bindendes Protein^[21]
• RELA^[16]
• MAPK8^{[22][23][24][25][26][27][28][29]}
• NCOR2^[30]
• RFWD2^[31][32]
• PIN1^[33]
• FOSL1^[14]
• SMAD3^[34][35][36]
• ASCC3^[37]
• TFIIB^[21]
• CSNK2A2^[38]
• CSNK2A1^[38]
• STAT1^[39]
• BCL6^[40]
• BCL3^[41]
• Receptor androgénico^[42]
• STAT3^[39]
• ETS2^[43]
• ATF3^[44][45][10]
• NACA^[46]
• COPS5^[47]
• DDIT3^[48]
• RBM39^[49]
• NCOA1^[50][51][52]
• MyoD^[53]
• RUNX2^[54][55]
• RUNX1^[54][55]

Einzelnachweise

1. Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M: The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. In: Cell. 54. Jahrgang, Nr. 4, August 1988, S. 541–52, doi:10.1016/0092-8674(88)90076-1, PMID 3135940.
2. Vogt PK: Fortuitous convergences: the beginnings of JUN. In: Nature Reviews Cancer. 2. Jahrgang, Nr. 6, Juni 2002, S. 465–9, doi:10.1038/nrc818, PMID 12189388.
3. Wisdom R, Johnson RS, Moore C: c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. In: The EMBO Journal. 18. Jahrgang, Nr. 1, Januar 1999, S. 188–97, doi:10.1093/emboj/18.1.188, PMID 9878062, PMC 1171114 (freier Volltext).
4. M. Pessah, C. Prunier, J. Marais, N. Ferrand, A. Mazars, F. Lallemand, J. M. Gauthier, A. Atfi: c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity. In: Proceedings of the National Academy of Sciences. Band 98, Nummer 11, Mai 2001, S. 6198–6203, doi:10.1073/pnas.101579798, PMID 11371641, PMC 33445 (freier Volltext).
5. A. Verger, E. Buisine, S. Carrère, R. Wintjens, A. Flourens, J. Coll, D. Stéhelin, M. Duterque-Coquillaud: Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation. In: The Journal of biological chemistry. Band 276, Nummer 20, Mai 2001, S. 17181–17189, doi:10.1074/jbc.M010208200, PMID 11278640.
6. J. Nishitani, T. Nishinaka, C. H. Cheng, W. Rong, K. K. Yokoyama, R. Chiu: Recruitment of the retinoblastoma protein to c-Jun enhances transcription activity mediated through the AP-1 binding site. In: The Journal of biological chemistry. Band 274, Nummer 9, Februar 1999, S. 5454–5461, PMID 10026157.
7. Y. Sano, F. Tokitou, P. Dai, T. Maekawa, T. Yamamoto, S. Ishii: CBP alleviates the intramolecular inhibition of ATF-2 function. In: The Journal of biological chemistry. Band 273, Nummer 44, Oktober 1998, S. 29098–29105, PMID 9786917.
8. C. L. Newell, A. B. Deisseroth, G. Lopez-Berestein: Interaction of nuclear proteins with an AP-1/CRE-like promoter sequence in the human TNF-alpha gene. In: Journal of leukocyte biology. Band 56, Nummer 1, Juli 1994, S. 27–35, PMID 8027667.
9. C. J. Kara, H. C. Liou, L. B. Ivashkiv, L. H. Glimcher: A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain. In: Molecular and cellular biology. Band 10, Nummer 4, April 1990, S. 1347–1357, PMID 2320002, PMC 362236 (freier Volltext).
10. T. Hai, T. Curran: Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. In: Proceedings of the National Academy of Sciences. Band 88, Nummer 9, Mai 1991, S. 3720–3724, PMID 1827203, PMC 51524 (freier Volltext).
11. H. Zhong, J. Zhu, H. Zhang, L. Ding, Y. Sun, C. Huang, Q. Ye: COBRA1 inhibits AP-1 transcriptional activity in transfected cells. In: Biochemical and biophysical research communications. Band 325, Nummer 2, Dezember 2004, S. 568–573, doi:10.1016/j.bbrc.2004.10.079, PMID 15530430.
12. Y. F. Hu, R. Li: JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction. In: Genes & development. Band 16, Nummer 12, Juni 2002, S. 1509–1517, doi:10.1101/gad.995502, PMID 12080089, PMC 186344 (freier Volltext).
13. T. Ito, M. Yamauchi, M. Nishina, N. Yamamichi, T. Mizutani, M. Ui, M. Murakami, H. Iba: Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers. In: The Journal of biological chemistry. Band 276, Nummer 4, Januar 2001, S. 2852–2857, doi:10.1074/jbc.M009633200, PMID 11053448.
14. P. Pognonec, K. E. Boulukos, C. Aperlo, M. Fujimoto, H. Ariga, A. Nomoto, H. Kato: Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity. In: Oncogene. Band 14, Nummer 17, Mai 1997, S. 2091–2098, doi:10.1038/sj.onc.1201046, PMID 9160889.
15. J. N. Glover, S. C. Harrison: Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. In: Nature. Band 373, Nummer 6511, Januar 1995, S. 257–261, doi:10.1038/373257a0, PMID 7816143.
16. X. Yang, Y. Chen, D. Gabuzda: ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-kappaB. In: The Journal of biological chemistry. Band 274, Nummer 39, September 1999, S. 27981–27988, PMID 10488148.
17. N. Nomura, Y. L. Zu, T. Maekawa, S. Tabata, T. Akiyama, S. Ishii: Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. In: The Journal of biological chemistry. Band 268, Nummer 6, Februar 1993, S. 4259–4266, PMID 8440710.
18. T. Finkel, J. Duc, E. R. Fearon, C. V. Dang, G. F. Tomaselli: Detection and modulation in vivo of helix-loop-helix protein-protein interactions. In: The Journal of biological chemistry. Band 268, Nummer 1, Januar 1993, S. 5–8, PMID 8380166.
19. R. Venugopal, A. K. Jaiswal: Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. In: Oncogene. Band 17, Nummer 24, Dezember 1998, S. 3145–3156, doi:10.1038/sj.onc.1202237, PMID 9872330.
20. J. Westermarck, C. Weiss, R. Saffrich, J. Kast, A. M. Musti, M. Wessely, W. Ansorge, B. Séraphin, M. Wilm, B. C. Valdez, D. Bohmann: The DEXD/H-box RNA helicase RHII/Gu is a co-factor for c-Jun-activated transcription. In: The EMBO journal. Band 21, Nummer 3, Februar 2002, S. 451–460, PMID 11823437, PMC 125820 (freier Volltext).
21. C. C. Franklin, A. V. McCulloch, A. S. Kraft: In vitro association between the Jun protein family and the general transcription factors, TBP and TFIIB. In: The Biochemical journal. Band 305 ( Pt 3), Februar 1995, S. 967–974, PMID 7848298, PMC 1136352 (freier Volltext).
22. T. Ishitani, G. Takaesu, J. Ninomiya-Tsuji, H. Shibuya, R. B. Gaynor, K. Matsumoto: Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. In: The EMBO journal. Band 22, Nummer 23, Dezember 2003, S. 6277–6288, doi:10.1093/emboj/cdg605, PMID 14633987, PMC 291846 (freier Volltext).
23. H. Nishitoh, M. Saitoh, Y. Mochida, K. Takeda, H. Nakano, M. Rothe, K. Miyazono, H. Ichijo: ASK1 is essential for JNK/SAPK activation by TRAF2. In: Molecular cell. Band 2, Nummer 3, September 1998, S. 389–395, PMID 9774977.
24. B. Dérijard, M. Hibi, I. H. Wu, T. Barrett, B. Su, T. Deng, M. Karin, R. J. Davis: JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. In: Cell. Band 76, Nummer 6, März 1994, S. 1025–1037, PMID 8137421.
25. O. Yazgan, C. M. Pfarr: Regulation of two JunD isoforms by Jun N-terminal kinases. In: The Journal of biological chemistry. Band 277, Nummer 33, August 2002, S. 29710–29718, doi:10.1074/jbc.M204552200, PMID 12052834.
26. K. Tada, T. Okazaki, S. Sakon, T. Kobarai, K. Kurosawa, S. Yamaoka, H. Hashimoto, T. W. Mak, H. Yagita, K. Okumura, W. C. Yeh, H. Nakano: Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. In: The Journal of biological chemistry. Band 276, Nummer 39, September 2001, S. 36530–36534, doi:10.1074/jbc.M104837200, PMID 11479302.
27. C. F. Meyer, X. Wang, C. Chang, D. Templeton, T. H. Tan: Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating kappaB enhancer activation. In: The Journal of biological chemistry. Band 271, Nummer 15, April 1996, S. 8971–8976, PMID 8621542.
28. E. Cano, C. A. Hazzalin, E. Kardalinou, R. S. Buckle, L. C. Mahadevan: Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction. In: Journal of cell science. Band 108 ( Pt 11), November 1995, S. 3599–3609, PMID 8586671.
29. C. Tournier, A. J. Whitmarsh, J. Cavanagh, T. Barrett, R. J. Davis: Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. In: Proceedings of the National Academy of Sciences. Band 94, Nummer 14, Juli 1997, S. 7337–7342, PMID 9207092, PMC 23822 (freier Volltext).
30. S. K. Lee, J. H. Kim, Y. C. Lee, J. Cheong, J. W. Lee: Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor. In: The Journal of biological chemistry. Band 275, Nummer 17, April 2000, S. 12470–12474, PMID 10777532.
31. S. K. Lee, J. H. Kim, Y. C. Lee, J. Cheong, J. W. Lee: Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor. In: The Journal of biological chemistry. Band 275, Nummer 17, April 2000, S. 12470–12474, PMID 10777532.
32. E. Bianchi, S. Denti, R. Catena, G. Rossetti, S. Polo, S. Gasparian, S. Putignano, L. Rogge, R. Pardi: Characterization of human constitutive photomorphogenesis protein 1, a RING finger ubiquitin ligase that interacts with Jun transcription factors and modulates their transcriptional activity. In: The Journal of biological chemistry. Band 278, Nummer 22, Mai 2003, S. 19682–19690, doi:10.1074/jbc.M212681200, PMID 12615916.
33. G. M. Wulf, A. Ryo, G. G. Wulf, S. W. Lee, T. Niu, V. Petkova, K. P. Lu: Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. In: The EMBO journal. Band 20, Nummer 13, Juli 2001, S. 3459–3472, doi:10.1093/emboj/20.13.3459, PMID 11432833, PMC 125530 (freier Volltext).
34. Y. Zhang, X. H. Feng, R. Derynck: Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. In: Nature. Band 394, Nummer 6696, August 1998, S. 909–913, doi:10.1038/29814, PMID 9732876.
35. F. Verrecchia, M. Pessah, A. Atfi, A. Mauviel: Tumor necrosis factor-alpha inhibits transforming growth factor-beta/Smad signaling in human dermal fibroblasts via AP-1 activation. In: The Journal of biological chemistry. Band 275, Nummer 39, September 2000, S. 30226–30231, doi:10.1074/jbc.M005310200, PMID 10903323.
36. N. T. Liberati, M. B. Datto, J. P. Frederick, X. Shen, C. Wong, E. M. Rougier-Chapman, X. F. Wang: Smads bind directly to the Jun family of AP-1 transcription factors. In: Proceedings of the National Academy of Sciences. Band 96, Nummer 9, April 1999, S. 4844–4849, PMID 10220381, PMC 21779 (freier Volltext).
37. D. J. Jung, H. S. Sung, Y. W. Goo, H. M. Lee, O. K. Park, S. Y. Jung, J. Lim, H. J. Kim, S. K. Lee, T. S. Kim, J. W. Lee, Y. C. Lee: Novel transcription coactivator complex containing activating signal cointegrator 1. In: Molecular and cellular biology. Band 22, Nummer 14, Juli 2002, S. 5203–5211, PMID 12077347, PMC 139772 (freier Volltext).
38. Y. Yamaguchi, T. Wada, F. Suzuki, T. Takagi, J. Hasegawa, H. Handa: Casein kinase II interacts with the bZIP domains of several transcription factors. In: Nucleic acids research. Band 26, Nummer 16, August 1998, S. 3854–3861, PMID 9685505, PMC 147779 (freier Volltext).
39. X. Zhang, M. H. Wrzeszczynska, C. M. Horvath, J. E. Darnell: Interacting regions in Stat3 and c-Jun that participate in cooperative transcriptional activation. In: Molecular and cellular biology. Band 19, Nummer 10, Oktober 1999, S. 7138–7146, PMID 10490649, PMC 84707 (freier Volltext).
40. F. H. Vasanwala, S. Kusam, L. M. Toney, A. L. Dent: Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene. In: Journal of Immunology (Baltimore, Md. : 1950). Band 169, Nummer 4, August 2002, S. 1922–1929, PMID 12165517.
41. S. Y. Na, J. E. Choi, H. J. Kim, B. H. Jhun, Y. C. Lee, J. W. Lee: Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation. In: The Journal of biological chemistry. Band 274, Nummer 40, Oktober 1999, S. 28491–28496, PMID 10497212.
42. N. Sato, M. D. Sadar, N. Bruchovsky, F. Saatcioglu, P. S. Rennie, S. Sato, P. H. Lange, M. E. Gleave: Androgenic induction of prostate-specific antigen gene is repressed by protein-protein interaction between the androgen receptor and AP-1/c-Jun in the human prostate cancer cell line LNCaP. In: The Journal of biological chemistry. Band 272, Nummer 28, Juli 1997, S. 17485–17494, PMID 9211894.
43. J. P. Basuyaux, E. Ferreira, D. Stéhelin, G. Butticè: The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA-dependent and -independent manner. In: The Journal of biological chemistry. Band 272, Nummer 42, Oktober 1997, S. 26188–26195, PMID 9334186.
44. A. G. Pearson, C. W. Gray, J. F. Pearson, J. M. Greenwood, M. J. During, M. Dragunow: ATF3 enhances c-Jun-mediated neurite sprouting. In: Brain research. Molecular brain research. Band 120, Nummer 1, Dezember 2003, S. 38–45, PMID 14667575.
45. B. P. Chen, C. D. Wolfgang, T. Hai: Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10. In: Molecular and cellular biology. Band 16, Nummer 3, März 1996, S. 1157–1168, PMID 8622660, PMC 231098 (freier Volltext).
46. A. Moreau, W. V. Yotov, F. H. Glorieux, R. St-Arnaud: Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. In: Molecular and cellular biology. Band 18, Nummer 3, März 1998, S. 1312–1321, PMID 9488446, PMC 108844 (freier Volltext).
47. F. X. Claret, M. Hibi, S. Dhut, T. Toda, M. Karin: A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. In: Nature. Band 383, Nummer 6599, Oktober 1996, S. 453–457, doi:10.1038/383453a0, PMID 8837781.
48. M. Ubeda, M. Vallejo, J. F. Habener: CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins. In: Molecular and cellular biology. Band 19, Nummer 11, November 1999, S. 7589–7599, PMID 10523647, PMC 84780 (freier Volltext).
49. D. J. Jung, S. Y. Na, D. S. Na, J. W. Lee: Molecular cloning and characterization of CAPER, a novel coactivator of activating protein-1 and estrogen receptors. In: The Journal of biological chemistry. Band 277, Nummer 2, Januar 2002, S. 1229–1234, doi:10.1074/jbc.M110417200, PMID 11704680.
50. S. K. Lee, S. L. Anzick, J. E. Choi, L. Bubendorf, X. Y. Guan, Y. K. Jung, O. P. Kallioniemi, J. Kononen, J. M. Trent, D. Azorsa, B. H. Jhun, J. H. Cheong, Y. C. Lee, P. S. Meltzer, J. W. Lee: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. In: The Journal of biological chemistry. Band 274, Nummer 48, November 1999, S. 34283–34293, PMID 10567404.
51. S. K. Lee, S. Y. Na, S. Y. Jung, J. E. Choi, B. H. Jhun, J. Cheong, P. S. Meltzer, Y. C. Lee, J. W. Lee: Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2. In: Molecular endocrinology (Baltimore, Md.). Band 14, Nummer 6, Juni 2000, S. 915–925, doi:10.1210/mend.14.6.0471, PMID 10847592.
52. S. K. Lee, H. J. Kim, S. Y. Na, T. S. Kim, H. S. Choi, S. Y. Im, J. W. Lee: Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits. In: The Journal of biological chemistry. Band 273, Nummer 27, Juli 1998, S. 16651–16654, PMID 9642216.
53. E. Bengal, L. Ransone, R. Scharfmann, V. J. Dwarki, S. J. Tapscott, H. Weintraub, I. M. Verma: Functional antagonism between c-Jun and MyoD proteins: a direct physical association. In: Cell. Band 68, Nummer 3, Februar 1992, S. 507–519, PMID 1310896.
54. J. Hess, D. Porte, C. Munz, P. Angel: AP-1 and Cbfa/runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element. In: The Journal of biological chemistry. Band 276, Nummer 23, Juni 2001, S. 20029–20038, doi:10.1074/jbc.M010601200, PMID 11274169.
55. R. C. D'Alonzo, N. Selvamurugan, G. Karsenty, N. C. Partridge: Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation. In: The Journal of biological chemistry. Band 277, Nummer 1, Januar 2002, S. 816–822, doi:10.1074/jbc.M107082200, PMID 11641401.