АР-1 (activating protein-1
в переводе на русский:
активирующий белок-1
) - это собирательный термин, относящийся к
гетеродимерным факторам
транскрипции, состоящим из субъединиц
(c-Jun, JunB, и JunD) и
(c-Fos, FosB, Fra1, и Fra2). Помимо этого гетеродимерные комплексы с белками AP-1 (преимущественно с белками Jun) могут образовывать некоторые члены подсемейств
, а также выступающие в качестве
репрессора
AP-1 белки
, которые связываются с общим сайтом ДНК, сайтом связывания АР-1.
Жизненно важную роль в активации генов-мишеней АР-1, тем самым способствуя выживанию клеток при ответе на
стресс
играет белок
(который структурно и функционально гомологичен
p53
, но, по-видимому, также обладает рядом свойств, отличных от р53, которые могут быть связаны с различной специфичностью к
промотору
). В частности, TAp73 активирует рост клеток путем прямого связывания с c-Jun на промоторах-мишенях AP-1, что приводит к увеличению их доступности для других членов семейства AP-1
.
Примечания
Hess J., Angel P., Schorpp-Kistner M.
AP-1 subunits: quarrel and harmony among siblings
(англ.)
//
(англ.)
(
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(англ.)
(
, 2004. —
Vol. 117
,
no. Pt 25
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P. 5965—5973
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doi
:
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.
Beisaw, A., Kuenne, C., Günther, S., Dallmann, J., Wu, C. C., Bentsen, M., ... & Stainier, D. (2020). AP-1 Contributes to Chromatin Accessibility to Promote Sarcomere Disassembly and Cardiomyocyte Protrusion during Zebrafish Heart Regeneration. Circulation Research.
PMID
PMC
(available on 2021-06-05)
doi
:
Shaulian, E., & Karin, M. (2001). AP-1 in cell proliferation and survival. Oncogene, 20(19), 2390-2400.
PMID
doi
:
Verde, P., Casalino, L., Talotta, F., Yaniv, M., & Weitzman, J. B. (2007). Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters. Cell cycle, 6(21), 2633-2639.
PMID
doi
:
Thomsen, M. K., Bakiri, L., Hasenfuss, S. C., Wu, H., Morente, M., & Wagner, E. F. (2015). Loss of JUNB/AP-1 promotes invasive prostate cancer. Cell Death & Differentiation, 22(4), 574-582.
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:
PMC
PMID
Han, R., Li, L., Ugalde, A. P., Tal, A., Manber, Z., Barbera, E. P., ... & Agami, R. (2018). Functional CRISPR screen identifies AP1-associated enhancer regulating FOXF1 to modulate oncogene-induced senescence. Genome biology, 19(1), 19: 118(2018)
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:
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PMID
Mirzaei, H., Khodadad, N., Karami, C., Pirmoradi, R., & Khanizadeh, S. (2020). The AP‐1 pathway; A key regulator of cellular transformation modulated by oncogenic viruses. Reviews in Medical Virology, 30(1), e2088.
PMID
doi
:
Martínez-Zamudio, R.I., Roux, P., de Freitas, J.A.N. et al. (2020). AP-1 imprints a reversible transcriptional programme of senescent cells. Nat Cell Biol
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PMC
PMID
Shaulian, E., & Karin, M. (2002). AP-1 as a regulator of cell life and death. Nature cell biology, 4(5), E131-E136.
PMID
doi
:
Yang A, Walker N, Bronson R, et al. (2000). p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature. 404(6773): 99–103.
doi
:
PMID
Wang, C., Teo, C. R., & Sabapathy, K. (2020). p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? International journal of molecular sciences, 21(4), 1346.
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:
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Subramanian, D., Bunjobpol, W., & Sabapathy, K. (2015). Interplay between TAp73 protein and selected activator protein-1 (AP-1) family members promotes AP-1 target gene activation and cellular growth. Journal of Biological Chemistry, 290(30), 18636-18649.
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Литература
Ye, N., Ding, Y., Wild, C., Shen, Q., & Zhou, J. (2014). Small molecule inhibitors targeting activator protein 1 (AP-1) miniperspective. Journal of medicinal chemistry, 57(16), 6930-6948.
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PMID
Eferl, R., & Wagner, E. F. (2003). AP-1: a double-edged sword in tumorigenesis. Nature Reviews Cancer, 3(11), 859-868.
PMID
doi
:
Sundqvist, A., Vasilaki, E., Voytyuk, O., Bai, Y., Morikawa, M., Moustakas, A., ... & van Dam, H. (2020). TGFβ and EGF signaling orchestrates the AP-1-and p63 transcriptional regulation of breast cancer invasiveness. Oncogene, 39(22), 4436-4449.
doi
:
PMC
PMID
Hseu, Y. C., Vudhya Gowrisankar, Y., Chen, X. Z., Yang, Y. C., & Yang, H. L. (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. Oxidative Medicine and Cellular Longevity, 2020.
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PMID
Kleiner, J., Hollborn, M., Wiedemann, P., & Bringmann, A. (2018). Activator protein-1 contributes to the NaCl-induced expression of VEGF and PlGF in RPE cells. Molecular vision, 24, 647.
PMC
PMID
Anuchapreeda, S., Rungrojsakul, M., Tima, S., Chiampanichayakul, S., & Krig, S. R. (2019). Co-activation of WT1 and AP-1 proteins on WT1 gene promoter to induce WT1 gene expression in K562 cells. Cellular signalling, 53, 339-347.
PMID
doi
:
Hesari, A., Ghasemi, F., Salarinia, R., Biglari, H., Tabar Molla Hassan, A., Abdoli, V., & Mirzaei, H. (2018). Effects of curcumin on NF‐κB, AP‐1, and Wnt/β‐catenin signaling pathway in hepatitis B virus infection. Journal of cellular biochemistry, 119(10), 7898-7904.
PMID
doi
:
Yang, X. J., Liu, F., Feng, N., Ding, X. S., Chen, Y., Zhu, S. X., ... & Feng, X. F. (2020). Berberine Attenuates Cholesterol Accumulation in Macrophage Foam Cells by Suppressing AP-1 Activity and Activation of the Nrf2/HO-1 Pathway. Journal of Cardiovascular Pharmacology, 75(1), 45-53.
PMID
doi
:
Huang, Y., Miao, Z., Hu, Y., Yuan, Y., Zhou, Y., Wei, L., ... & Lu, N. (2017). Baicalein reduces angiogenesis in the inflammatory microenvironment via inhibiting the expression of AP-1. Oncotarget, 8(1), 883.
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Ozolinš, T. R. (2019). Regulation and Control of AP-1 Binding Activity in Embryotoxicity. In Developmental Toxicology (pp. 375-388). Humana, New York, NY.
PMID
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Atsaves, V., Leventaki, V., Rassidakis, G. Z., & Claret, F. X. (2019). AP-1 transcription factors as regulators of immune responses in cancer. Cancers, 11(7), 1037.
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PMC
PMID
Gao, F., Zhou, L., Li, M., Liu, W., Yang, S., & Li, W. (2020). Inhibition of ERKs/Akt-Mediated c-Fos Expression Is Required for Piperlongumine-Induced Cyclin D1 Downregulation and Tumor Suppression in Colorectal Cancer Cells. OncoTargets and therapy, 13, 5591.
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Bejjani, F., Evanno, E., Zibara, K., Piechaczyk, M., & Jariel-Encontre, I. (2019). The AP-1 transcriptional complex: Local switch or remote command?. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1872(1), 11-23.
PMID
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Yang, C. M., Lin, C. C., Yang, C. C., Cho, R. L., & Hsiao, L. D. (2020). Mevastatin-Induced AP-1-Dependent HO-1 Expression Suppresses Vascular Cell Adhesion Molecule-1 Expression and Monocyte Adhesion on Human Pulmonary Alveolar Epithelial Cells Challenged with TNF-α. Biomolecules, 10(3), 381.
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Gazon, H., Barbeau, B., Mesnard, J. M., & Peloponese Jr, J. M. (2018). Hijacking of the AP-1 Signaling Pathway during Development of ATL. Frontiers in microbiology, 8, 2686.
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Jameson, N. M., Ma, J., Benitez, J., Izurieta, A., Han, J. Y., Mendez, R., ... & Furnari, F. (2019). Intron 1–Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins. Molecular Cancer Research, 17(11), 2208-2220.
doi
:
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Cao, L., Liu, Y., Wang, D., Huang, L., Li, F., Liu, J., ... & Zhang, Y. (2018). MiR-760 suppresses human colorectal cancer growth by targeting BATF3/AP-1/cyclinD1 signaling. Journal of Experimental & Clinical Cancer Research, 37(1), 1-14.
doi
:
PMC
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BATF3 образует комплекс с c-Jun в составе AP-1 на промоторе
циклина D1
и контролирует экспрессию циклина D1