FOS, JUN, AND AP-1 IN THE NERVOUS SYSTEM 
The CIE genes c -fos and c -jun encode nuclear phosphoproteins, Fos and Jun, 
respectively, that are components of the transcription factor activator protein-1 
(AP-1) (reviewed in Curran and Franza 1988). Fos and Jun dimerize via a 
leucine zipper-motif, an a-helical domain within both proteins that contains a 
heptad repeat of leucine residues (Landschultz et al. 1988). The dimeric 
complexes bind cooperatively to the AP-1 DNA consensus sequence 
(TGACTCA) via domains rich in basic amino acids. Fos and Jun both contain 
such a domain; therefore, each protein in the complex provides a half site for 
DNA binding. The AP-1 sequence is known to be essential for both basal and 
stimulated expression of some genes, and AP-1 binding at this element can 
modulate transcriptional activity (reviewed in Curran and Franza 1988; Morgan 
and Curran 1991a). 
Several genes have been described that are related closely to either c -fos or 
c -jun (e.g., /ra-1 , fra- 2, fos- B, jun- B, jun-D). The protein products can also 
participate in AP-1 dimeric complexes (reviewed in Kerppola and Curran 1991). 
In general, all Jun family members can dimerize with all Fos family members. 
In addition, all Jun (but not Fos) family members can form heterodimers and 
homodimers with themselves, although the apparent affinity of these complexes 
for the AP-1 site is lower than that of Fos family-Jun family heterodimers. The 
situation has become more complicated with the discovery that the leucine- 
zipper and basic DNA-binding motifs are present in several other families of 
DNA-binding proteins. This so-called basic-zipper family includes such proteins 
as the cyclic AMP response element binding proteins (CREBs) and the 
activating transcription factors (ATFs). These proteins interact with DNA 
sequences other than the AP-1 consensus, such as the cyclic AMP response 
element (CRE) (TGACGTCA) (Hai and Curran 1991; Kerppola and Curran 
1991). Furthermore, CREBs and ATFs form dimers with themselves as well as 
with selective members of the Fos and Jun families (Hai and Curran 1991). 
Thus, in some cases members of the Fos and Jun families may be components 
of an AP-1 complex, whereas in other circumstances they may be part of a 
complex interacting with a CRE. Obviously, this situation provides for a 
considerable degree of mixing and matching and may be one way that diversity 
is generated within the CIE response. 
A second feature of the CIE gene response is that it has a temporal component. 
In the rodent nervous system, pentylenetetrazole (PTZ) seizures elicit a rapid 
and transient increase in the mRNAs encoding c -fos and c -jun (Morgan et al. 
1987; Sonnenberg etal. 1989a, 1989b); fos and jun mRNAs reach maximum 
values within 30 to 60 minutes following seizure and subsequently decline to 
basal values by 2 to 3 hours. As anticipated, Fos accumulates in the brain for 
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