JUN gene

The JUN gene (Jun-stands for: protooncogene, AP-1 transcription factor subunit) is a protein-coding gene located on chromosome 1p32.1. This gene is intronless. Genes on the chromosomal 1p32-p31 region are involved in both translocations and deletions in human malignancies. An important paralog of this gene is JUN-D.

The JUN gene is the putative transforming gene of avian sarcoma virus 17 and encodes a protein that is very similar to the viral protein and interacts directly with specific target DNA sequences to regulate gene expression.

The signaling pathways associated with this gene include the Toll-like receptor 7/8 cascade (TLR7/8) and prolactin signaling.

The JUN gene encodes a transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (Qing J et al. 2000). Heterodimerizes with FOS family proteins to form an AP-1 transcriptional complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and its transcriptional activity. Together with FOSB, it plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L and inducing its transcription in response to activation of the TCR/CD3 signaling pathway (Baumann S et al. 2003). Promotes NR5A1 activity when phosphorylated by HIPK3, leading to increased steroidogenic gene expression upon stimulation of the cAMP signaling pathway (Lan HC et al. 2007). Involved in activated KRAS-mediated transcriptional activation of USP28 in colon cancer cells. Microbial infection: Binds to the viral BZLF1-Z promoter during Epstein-Barr virus (EBV) infection and activates viral BZLF1 expression.

When mammalian cells are exposed to DNA-damaging agents, a genetic response known as the UV response is activated. Since several previously identified UV-inducible genes contain AP-1 binding sites in their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents.

It was found that the expression of c-JUN and c-FOS, which encode proteins involved in the formation of the AP-1 complex, is induced by DNA-damaging UV. The c-JUN gene is much more responsive to UV than any of the others studied, including c-FOS. This preferential response of the c-JUN gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the DNA damage-induced signal transduction pathway (Devary Y et al. 1991).

Diseases associated with JUN include breast cancer and hematologic cancers.

1. Baumann S et al. (2003) An unexpected role for FosB in activation-induced cell death of T cells. Oncogene 22:1333-1339.
2. Lan HC et al. (2007) Cyclic AMP stimulates SF-1-dependent CYP11A1 expression through homeodomain-interacting protein kinase 3-mediated Jun N-terminal kinase and c-Jun phosphorylation. Mol Cell Biol 27:2027-2036.
3. Qing J et al. (2000) Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity. J Biol Chem 275:38802-38812.