c-JUN Protein – Transcription factor AP-1(JUN)

More Information about c-JUN Protein

C-Jun protein is coded by the JUN gene in humans. This protein, together with c-Fos protein forms the AP-1 transcription factor. Because of its interaction with c-Fos protein, c-Jun protein was initially identified as a Fos-binding protein p39. C-Jun protein is involved in the progression through G1 phase. The role of c-Jun protein is to regulate the activity of cyclin D1 activity which is a Rb kinase. Rb protein is a growth suppressor and is inactivated upon phosphorylation. When c-jun protein is absent, the expression of both p53 and p21 increases which results in cell cycle defects. For this reason, c-jun knockout is lethal. However, transgenic animals that contain c-jun protein that cannot undergo phosphorylation, can survive. In this case cells remain blocked in G1 phase. Upregulation of c-jun protein results in increased cell growth and proliferation which makes c-jun a proto-oncogenic protein.

C-Jun, along with c-Fos protein are highly regulated by different extracellular stimuli such as growth factors, pro-inflammatory cytokines, UV irradiation and oxidative cellular stress. Indeed, increased UV irradiation has been linked to elevated c-jun expression. ERK pathway has also been involved in c-jun expression regulation. Active ERK increases c-jun transcription as well as its stability. The mobilization of c-jun protein leads to the activation of it downstream target RCAK1 which enhances JNK activity. JNK is a kinase that binds to c-jun and double phosphorylates the protein on Ser-63 and Ser-73 of its transcriptional activation domain. Research suggests that the phosphorylation of c-jun protein on threonine 91 and 93 triggers c-jun pro-apoptotic activity . According to Ce et al., (2013) the phosphorylation of c-Jun at threonine 91 and threonine 93 is dependent of threonine 95 which suggested the combination of the three threonines as a sensitive amplifier of the JNK cascade. On the other hand, the JNK triggered survival pathway is inhibited by a survival pathway initiate by lithium which represses pro-apoptotic c-Jun/Ap-1 target genes.