induced in the absence of new protein synthesis distinguishes this set of genes 
from other genes, which may be called late-response genes (those that are 
expressed only if protein synthesis is allowed). Late-response genes are likely 
to be targets of transcription factors induced in the early part of the response. 
Subsequently, it was found that some of the lEGs are the cellular homologs 
of various retroviral oncogenes, including those for c-myc, c-fos, and c -jun 
(Cochran et al. 1984; Greenberg and Ziff 1984; Kelly et al. 1983; Lamph et al. 
1988; Muller et al. 1984; Ryder and Nathans 1988). Studies using antisense 
RNAs or oligonucleotides or antibodies have shown that the expression of c-fos 
and proto-oncogenes is necessary for the entry of quiescent fibroblasts into the 
cell cycle (Heikkila et al. 1987; Holt et al. 1986, 1988; Nishikura and Murray 
1 987; Wickstrom et al. 1 988). Microinjection or overexpression of c-myc by 
itself can potentiate the response of fibroblasts to other growth factors (Armelin 
et al. 1984; Kaczmarek et al. 1985). However, the finding that some lEGs can 
also be induced in cells such as neurons that have terminally differentiated 
indicates that the lEGs may have roles to play in processes other than cell 
growth regulation (Bravo et al. 1985; Curran and Morgan 1985; Greenberg 
et al. 1985; Kruijer et al. 1985). 
A wide variety of early-response genes have been identified from studies of 
serum growth factor-stimulated fibroblasts (Almendral et al. 1988; Cochran et al. 
1983; Lau and Nathans 1985, 1987; Lim et al. 1987). The total number of such 
genes is unclear but is probably in the range of 50 to 100. It can be seen from 
table 1 , which lists some of these genes, that there are a wide variety of gene 
products encoded by early-response genes. The two best characterized 
classes of such genes are transcription factor genes and secreted gene 
products. However, these are not the only type of gene products represented. 
Others such as p-actin and rho - B encode cytoskeletal and signal transduction 
molecules, respectively (Greenberg and Ziff 1984; Jahner and Hunter 1991a). 
The best characterized of these genes are transcription factors, which can be 
subdivided into several distinct categories. C-Fos and c-Jun are DNA-binding 
proteins that form heterodimers via their leucine zipper domains (Bohmann et 
al. 1987; Chiu et al. 1988; Landschulz et al. 1988; O’Shea et al. 1989; Rauscher 
et al. 1988a, 1988b; Vinson et al. 1989). Each of these genes has several 
related homologs (i.e., jun- B, jun- D, fra- 1 , and fos- B), which all can form 
heterodimers with opposite members of the family (Hai and Curran 1991 ; 
Halazonetis et al. 1988; Nakabeppu et al. 1988). In addition, c -jun can form a 
homodimer. Thus, the number of dimeric complexes formed in the cells by this 
family of gene products is larger than the number of genes that encode them. 
Almost all these homodimeric and heterodimeric complexes can bind to the 
activator protein-1 (AP-1) consensus site (TGACTCA), although the affinity of 
a given complex for a given site can vary (Hai and Curran 1991 ; Kovary and 
Bravo 1991 ; Ryseck and Bravo 1991). Different fos/jun complexes have 
4 
