Fos transcription factor

Heterdimers of the Jun and Fos transcription factor family constitute the transcription factor AP-1. Oxidative stress results in the increased transcription of the c-fos and c-jun genes although only a moderate induction of AP-1 occurs. 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

Dimerization of the Ce-zinc cluster transcription factors involves an a-helical coiled coil in the dimerization region. Coiled coils, often called leucine zippers, are also found in a large group of transcription factors that do not contain zinc. The leucine zipper is made up of two a helices in a coiled coil with every seventh residue leucine or some other large hydrophobic residue, such as isoleucine or valine. Leucine zipper transcription factors (b/zip) include factors characterized by heterodimerization, for example Fos and Jun. The a-helical DNA-binding motifs of the heterodimers recognize quite different base sequences and are continous with the a helices of the zipper. 

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. 

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. 

FIGURE 8.12 Direct phosphorylation of the STAT class of transcription factors. Through their SH2 domains, the p84Slalla and p91StaIlb associate with the receptor and become phosphorylated on tyrosine residues. They form a dimer (called the Sis-inducible factor, or SIF) that translocates to the nucleus, where it binds to a Sis-inducible element (SIE) and activates transcription of, for example, the c-fos gene. 

The immediate early gene product c-Fos (cellular feline osteosarcoma) has widely been used as a useful marker of neuronal activation. Fos, the protein encoded by the c-fos gene, is a transcription factor that triggers transcription in a cascade of cellular responses. To determine which neuron groups are involved in the response to PGD2 and/or adenosine, especially A2aR agonists, we examined Fos-immunoreactivity under these conditions (Scammell et al., 1998, 2001 Satoh et al., 1999). 

A range of cellular changes occurs following repeated drug administration and these processes may help to give rise to the withdrawal state [7]. New proteins that are synthesized include transcription factors in the Fos family, which increase responsiveness to the beneficial effects of drugs [8], These cellular changes coincide with the withdrawal state characterized by depression, irritability and anxiety. 

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