C-jun

Glover, J.N.M., Harrison, S.C. Crystal structure of the het-erodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature 373 257-261, 1995. 

Immediate early genes, e.g., c-fos, c-jun, and c-myc, are the first genes whose expression is induced in cells after a growth stimulus. They encode transcription factors and induce the expression of other growth-related genes. 

TAK-1 can also activate c-jun N-terminal kinase ( JNK) andp38 both of which are MAP kinases. JNK activates the transcription factor AP-1 and p38 is involved in mRNA stabilisation. This pathway is also capable of activating ERF-7 in dendritic cells in response to TLR-7 and TLR-9 ligands. 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

Gough DJ, Sabapathy K, Ko EY, Arthur HA, Schreiber RD, Trapani JA, Clarke CJ, Johnstone RW (2007) A novel c-Jun-dependent signal transduction pathway necessary for the transcriptional activation of interferon gamma response genes. J Biol Chem 282 938-946 Guidotti LG, Chisari EV (2001) Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 19 65-91... 

In some studies it has been shown that ITCs can cause increases in the pro-apoptotic caspase enzymes, caspase 3, caspase 8 or caspase However, in other work, specific caspase inhibitors failed to block cell death or cell detachment from the substratum . This suggests that caspase-activation may only be a bystander event, or may only occur after the initiating event of a block in the cell cycle. Indeed, although expression of c-Jun amino-terminal kinase (INK) in response to ITCs has been linked to the pro-apoptotic process, it remains entirely possible that this is a parallel signalling pathway, more closely related to the induction of Phase 1 or Phase 2 enzymes than to the... 

Subsequent studies have confirmed that the reason for this discrepancy is that the rat is able to rapidly metabolise P-carotene to retinol in the intestine, through the action of intestinal dioxygenase. In contrast humans absorb P-carotene systemically such that plasma levels of P-carotene increase to levels not found in the rodent. A more appropriate animal model is the ferret, which shows a similar metabolism to humans. High levels of plasma P-carotene in the ferret induce the cellular transcription factors c-fos and c-jun, and squamous metaplasia is seen in the lung with or without exposure to cigarette smoke (SCF, 2000). Even after the investment of all these resources it has not been possible for the EU Scientific Committee on Food to set an ADI. 

Murasawa S, Matsubara H, Mori Y, et al. Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Racl-mediated c-Jun NH2-terminal kinase. J Biol Chem 2000 275(35) 26856-26863. 

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