Jun proteins are very similar in their basic DNA- 
binding regions, in their leucine zipper sequences, 
and in the putative transcription-activation seg- 
ments. Each of the proteins forms homodimers (or 
heterodimers with another Jun protein) and binds 
weakly to an AP-1 site or cAMP response element 
(CRE) in DNA. However, in the presence of Fos or 
Fra-1 the binding affinity is greatly enhanced. Thus 
Jun/Fos or Jun/Fra-1 heterodimers are the most ac- 
tive binding species, and the DNA-binding site spec- 
ificity of the various Jun/Fos or Jun/Fra-1 hetero- 
dimers is very similar. 
The current model for the binding of Fos/Jun 
heterodimers to an AP-1 site or CRE pictures the 
monomers held together by a coiled coil structure 
involving their leucine repeat helices, with their 
basic regions contacting symmetrical halves of the 
binding site. To test the prediction that in the 
Fosjun heterodimer the basic region of Fos confers 
specific DNA-binding properties equivalent to those 
of the basic region of Jun, truncated Fos/Jun chi- 
meric proteins were prepared, consisting of the 
basic region of one protein joined to the leucine re- 
PUBLICATIONS 
peat of the other. Heterodimers with mixed Fos and 
Jun leucine repeat segments showed high-affinity 
binding to the AP-1 site or CRE, whether they con- 
tained two basic regions from Jun, two basic re- 
gions from Fos, or one from each source. Hetero- 
dimers with two Fos basic regions showed 
somewhat greater affinity for the CRE and AP-1 site 
than the heterodimer with two Jun basic regions. 
The DNA sequence specificity and the purine and 
phosphate DNA contact sites for each heterodimer 
were similar. Thus in the Fos-Jun heterodimer the 
basic region of Fos contributes specific DNA-bind- 
ing properties equivalent to those of Jun. These re- 
sults support a model in which the Fos and Jun 
basic regions of the Fos-Jun heterodimer each inter- 
act with symmetrical DNA half-sites; the differences 
in DNA binding of Fos -I- Jun versus Jun or Fos 
alone are due to the variable dimerization proper- 
ties of Fos and Jun. 
Dr. Nathans is also University Professor of Molec- 
ular Biology and Genetics at The Johns Hopkins 
University School of Medicine. 
Articles 
Christy, B.A., Lau, L.F., and Nathans, D. 1988. A gene activated in mouse 3T3 cells by serum growth factors 
encodes a protein with "zinc finger" sequences. Proc Natl Acad Set USA 85:7857-7861. 
Hartzell, S., Ryder, K., Lanahan, A. , Lau, L.F. , and Nathans, D. 1989- A growth factor-responsive gene of mu- 
rine BALB/c 3T3 cells encodes a protein homologous to human tissue factor. Mol Cell Biol 9:2567-2573. 
Hazel, TG., Nathans, D., and Lau, L.F.. 1988. A gene inducible by serum growth factors encodes a member of 
the steroid and thyroid hormone receptor superfamily. Proc Natl Acad Set USA 85 :8444-8448. 
Nakabeppu, Y , Ryder, K., and Nathans, D. 1988. DNA binding activities of three murine Jun proteins: stimu- 
lation by Fos. Cell 55:907-915^ 
Nathans, D., Lau, L.F., Christy, B., Hartzell, S., Nakabeppu, Y, and Ryder, K. 1988. Genomic response to 
growth factors. Cold Spring Harb Symp Quant Biol 53:893-900. 
Ryder, K., Lanahan, A. , Perez-Albuerne, E., and Nathans, D. 1989. Jun-D: a third member of the Jun gene 
family. Proc Natl Acad Sci USA 86: 1500-1503. 
Ryder, K., and Nathans, D. 1988. Induction of protooncogene c-jun by serum growth factors. Proc Natl Acad 
Sci USA 85:8464-8467. 
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