JUN Research Reagents

JUN Background

Jun was found as a novel oncoprotein encoded by a cellular insert in the genome of avian sarcoma virus 17 (ASV17), an acutely oncogenic retrovirus isolated from a spontaneous tumor in a chicken ^[1][2]. The human JUN gene encodes c-Jun highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. c-Jun contains a docking site for the Jun N-terminal kinases (JNKs) which phosphorylate Serines 63 and 73, thereby enhancing its transcriptional potential and stability ^[3]. And c-Jun can form either homo- or heterodimers with members of the Jun family ^[4]. Fos–Jun and Jun–Jun dimers form the transcription factor AP‐1, a dimeric transcription factor complex ^[4]. Growth factors, hormones, and a variety of environmental stresses activate mitogen-activated protein kinase (MAPK) cascades that enhance Jun/AP-1 activity through phosphorylation, thereby regulating cell proliferation, differentiation, transformation, and/or apoptosis ^[4]. Functional data suggest that c‐Jun is not only a target for activation by many of the extracellular stimuli but also plays a role in mediating the cellular response. Ron Wisdom et al. revealed that in fibroblasts, c‐Jun is required for progression through the G1 phase of the cell cycle, and c‐Jun protects cells from UV‐induced apoptosis and cooperates with NF‐kappa B to prevent apoptosis induced by tumor necrosis factor-alpha (TNFα) ^[5]. Phosphorylation of c‐Jun on serines 63 and 73 by JNK is required for the UV protective effects, but not for the ability to promote cell proliferation ^[5]. c-jun transcription is autoregulated by its own product Jun ^[6], which may be a mechanism for prolonging the signals from extracellular stimuli. And this mechanism has biological significance for the activity of c-jun in cancer ^[6][7]. Also, c-jun activities can be regulated by the ERK pathway. Constitutively active ERK increases c-jun transcription and stability through CREB and GSK3. This results in activated c-jun and its downstream targets such as RACK1 and cyclin D1. RACK1 can enhance JNK activity, and activated JNK signaling subsequently exerts regulation on c-jun activity ^[8].

[1] Cavalieri F, Ruscio T, et al. Isolation of three new avian sarcoma viruses: ASV 9, ASV 17, and ASV 25 [J]. Virology 1985, 143(2): 680-683.
[2] Maki Y, Bos TJ, et al. Avian sarcoma virus 17 carries the jun oncogene [J]. Proc. Natl. Acad. Sci. USA 1987, 84: 2848-2852.
[3] Smeal T, Binetruy B, et al. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73 [J]. 1991 Nature 354(6353): 494-496.
[4] Zenz R, Wagner EF. Jun signalling in the epidermis: From developmental defects to psoriasis and skin tumors [J]. Int J Biochem Cell Biol. 2006; 38(7):1043-9.
[5] Ron Wisdom, Randall S. Johnson, et al. c‐Jun regulates cell cycle progression and apoptosis by distinct mechanisms [J]. EMBO J (1999)18:188-197.
[6] Angel P, Hattori K, et al. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1 [J]. Cell. 1998, 55 (5): 875-85.
[7] Rotondo JC, Borghi A, et al. Association of Retinoic Acid Receptor β Gene With Onset and Progression of Lichen Sclerosus-Associated Vulvar Squamous Cell Carcinoma [J]. JAMA Dermatology. 2018, 154 (7): 819-823.
[8] Lopez-Bergami P, Huang C, et al. Rewired ERK-JNK signaling pathways in melanoma [J]. Cancer Cell. 2007, 11 (5): 447-60.