About Jun Proto-Oncogene / C-JUN:
The C-JUN protein, otherwise known as the Jun-Proto-Oncogene, is encoded in humans by the JUN gene and forms the AP-1 early response transcription factor in connection with the c-Fos proto-oncogene. It is the cellular homolog of oncoprotein v-jun (P05411) and is involved with both translocations and deletions in human malignancies. The intronless gene is mapped to 1p32-p31 and regulates gene expression through direct interactions with target DNA sequences.
The C-JUN protein is also referred to as JUN, AP-1, AP1, c-Jun, and p39. The function is reliant on regulations of diverse extracellular stimuli such as peptide growth factors, pro-inflammatory cytokines, oxidative and UV irradiation. C-JUN is self-regulated by its own Jun protein and binds to a high-affinity AP-1 binding site within the promoter region. Its list of external Ids includes OMIM: 165160 MGI: 96646 HomoloGene: 1679 GeneCards: JUN.
C-JUN regulation follows an ERK pathway, with active ERK increasing the CREB and GSK3. In turn, the activated C-JUNs targets including RACK1 and cyclin D1 enhances JNK activity to activate C-JUN protein activity. Through stimulating its own transcription, C-JUN mechanisms prolong the signals from extracellular stimuli, confirming its biological importance in cancer.
The double phosphorylation of the JNK pathway and phosphorylation-independent function generate a lethal gene knockout while phosphorylation serines 63 and 73, as well as threonine 91 and 93, enhance the transcription of the target genes.
C-JUN protein is present in the progression of the G1 phase of the cell cycle, with an absent C-JUN show resulting in G1 arrest while it also regulates the cyclin D1 Rb kinase growth suppressor.
C-JUN is a significant protein in the cellular proliferation and apoptosis of the endometrium within the menstrual cycle, affecting glandular epithelial cells and potentially preventing the stromal cells from entering the apoptosis in the secretory phase.
Overexpression of the C-JUN protein has been linked with metastatic lung tumours within non-small cell lung cancers while C-JUN is not only expressed in healthy functioning airways and alveolar epithelias. Overexpressions of C-JUN in MCF-7 cells has also been shown to accelerate the rate of aggression in breast cancer.
While overexpression of the C-JUN protein is heavily linked to tumour initiation and increased invasiveness, alternative activities of the protein can help suppress cell cycle inhibitor. For example, it can prevent methylation of p16, allowing the cyclin-dependent kinase inhibitor 2A, multiple tumour suppressor 1 to remain active.
The plant-derived alkaloid known as Tylophorine also aids cell cycle arrest through anti-cancer activity. The increased presence of the C-JUN protein is a mediator that actively supports Tylophorine to arrest G1 carcinoma cell courtesy of cyclin A2 downregulations.