Jun proto-oncogene, AP-1 transcription factor subunit
Jun proto-oncogene, AP-1 transcription factor subunit
Overview
Jun proto-oncogene, AP-1 transcription factor subunit (commonly JUN) encodes a major component of the activator protein-1 (AP-1) transcription factor complex. JUN is a nuclear transcriptional regulator that integrates signals from multiple upstream pathways, including MAPK signaling, PI3K/Akt signaling pathway, inflammatory cascades, and stress responses. By forming homo- or heterodimers with other AP-1 family proteins, JUN helps control gene expression programs involved in cell proliferation, differentiation, survival, migration, and inflammatory activation.
Biomedically, JUN is widely studied as a proto-oncogene because AP-1 activity can support tumor growth, invasion, and adaptation to stress. At the same time, JUN is also implicated in nonmalignant disease processes such as inflammation, fibrosis, and vascular remodeling. Its activity is often assessed in relation to downstream transcriptional programs involving MYC, STAT3, nuclear factor kappa B, B-cell lymphoma 2, Interleukin 1 beta, and matrix-remodeling genes such as MMP9, reflecting its role as a central signaling node rather than a disease-specific effector.
Recent Publications Focus
Below is a summary of the newest research publications targeting Jun proto-oncogene, AP-1 transcription factor subunit (sorted by publication date).
Recent studies have continued to place JUN at the center of stress-response, inflammatory, and oncogenic signaling networks. In a heatstroke rat model, transcriptomic and proteomic profiling of the hypothalamus identified Jun among three key genes/proteins with altered expression, alongside Hspb1 and Dnaja1. The integrated multi-omics analysis linked heatstroke-induced injury to pathways including endoplasmic reticulum protein processing, MAPK signaling, and apoptosis, and JUN expression changes were validated by qRT-PCR, Western blot, and immunohistochemistry. In a separate network pharmacology study of gut microbiota-derived metabolites in Alzheimer’s disease, JUN emerged as one of the central hub genes within an immune-inflammatory network that also included IL6, NFKB1, IL1B, CXCL8, PPARG, and FOS, with enrichment in immune-inflammatory responses, oxidative stress-related processes, apoptosis, and MAPK-, TNF-, NF-κB-, and NOD-like receptor-associated pathways.
In cancer-focused work, JUN was identified as a key node in multiple AP-1-centered regulatory networks. A human colon organoid model of APC/TP53 double knockout showed that AP-1 transcription factors, specifically FOS/JUN, regulate KIT expression through chromatin remodeling, supporting an AP-1/KIT signaling axis that promotes early colorectal tumorigenesis via MAPK and Wnt signaling. Another network pharmacology and docking study of the nutraceutical formulation Vernolac also highlighted JUN as a hub target among cancer-related proteins, together with Akt1, BCL2, CASP3, CTNNB1, EGFR, ESR1, HSP90AA1, IL6, SRC, STAT3, and TNF. That study associated the target set with cancer pathways related to apoptosis, immune modulation, oxidative stress, inflammation, cell proliferation, drug resistance, and treatment response, while also reporting selective antiproliferative activity of the extract in several cancer cell lines.
Additional publications further reinforced JUN’s role in inflammatory and immune-associated disease mechanisms. In IgA nephropathy, bioinformatic analysis identified JUN as one of six pyroptosis-related hub genes with high diagnostic accuracy, alongside BHLHE40, CEBPB, ACE2, IL1B, and CD14; these genes were associated with immune response, cell migration, inflammation-related signaling, and increased infiltration of CD8+ T cells, macrophages, and neutrophils. In rheumatoid arthritis, Murraya exotica extract was reported to suppress AP-1 activation by downregulating c-Fos and c-Jun, alongside inhibition of NF-κB signaling, and this effect was linked to reduced inflammation, oxidative stress, proliferation, and migration in collagen-induced arthritis rats and IL-1β-stimulated synovial cells. Finally, in bladder and colon cancer cells, AP-1 inhibition was investigated as a means to reduce CD46-mediated invasion, building on prior evidence that CD46 activates AP-1 phosphorylation to stimulate MMP9 expression.
Result PMIDs
- [PMID 41706704]
- [PMID 41805865]
- [PMID 42401564]
Target PMIDs
- [PMID 42049325]
- [PMID 42062033]
- [PMID 42135973]
- [PMID 42249966]
- [PMID 42384725]
- [PMID 42401564]
- [PMID 42406869]
- [PMID 42412186]