DNA they must first form homodimers or hetero- 
dimers via coiled-coil structures made up of leucine 
zipper domains. Certain other leucine zipper DNA- 
binding proteins have also been shown to form het- 
erodimers with Jun. To identify additional proteins 
that dimerize with the leucine zipper of Jun or Fos, 
Pierre Chevray (a graduate student in Dr. Nathans' 
laboratory, whose research is supported by the Na- 
tional Cancer Institute) has used a yeast genetic sys- 
tem described by Drs. Stanley Fields and Ok-kyu 
Song to clone mouse cDNAs encoding polypeptides 
that interact with the leucine zipper segment of 
c-Jun or c-Fos. 
Several proteins were identified, some showing 
interaction only with Jun or only with Fos. One of 
the proteins is a member of the ATF/CRFB fam- 
ily of transcription factors, probably the murine 
homologue of TAXREB67. Others are a- and j8- 
tropomyosins, which are known to form coiled-coil 
structures via extensive leucine zipper domains, 
and several are previously undescribed proteins 
with predicted potential to form coiled coils. In ad- 
dition, Dr. Timothy Schaefer (Associate in Dr. Na- 
thans' laboratory) has used the yeast system to iden- 
tify proteins that interact with Jun outside the 
zipper domain. 
Delayed-Early Genes 
To identify delayed-early genes in a systematic 
way. Dr. Anthony Lanahan (Associate in Dr. Nathans' 
laboratory) constructed a 3T3 cell cDNA library 
enriched in delayed-early cDNAs. As reported 
briefly last year, he selected by differential screen- 
ing cDNAs derived from mRNAs that are induced by 
serum with delayed-early kinetics. About 40% of the 
650 primary cDNA isolates are represented by 13 
different cDNAs. Partial or complete sequencing of 
the 13 cDNAs carried out by Dr. Lanahan and Dr. 
John Williams (an HHMI Postdoctoral Research Fel- 
low) revealed that 9 are related to known proteins 
and 4 are not. Among the former are cDNAs encod- 
ing the nonhistone chromosomal proteins HMGI(Y) 
and HMGI-C, adenine phosphoribosyltransferase 
(APRT), DNA polymerase 5, a protein related to hu- 
man macrophage migration inhibitory factor (MIF) , 
the murine homologue of CHIP28 (an integral 
membrane protein of human erythrocytes involved 
in water transport), and cyclin CYLl. On the as- 
sumption that most of the more abundant cDNA spe- 
cies have already been detected, one can estimate 
that several dozen delayed-early cDNAs in the col- 
lection remain to be characterized. Thus the de- 
layed-early gene response is likely to be at least as 
complex as the immediate-early gene response. 
Each of the delayed-early mRNAs so far identified 
appears or increases a few hours after cell stimula- 
tion by serum, PDGF, or FGF, well before the onset 
of serum-induced DNA synthesis, and the response is 
inhibited by cycloheximide and anisomycin. In 
each case gene transcription is stimulated by the 
growth factor. For some of the genes, potential bind- 
ing sites for immediate-early transcription factors 
have been detected upstream of the transcription 
start site. Studies are in progress to determine 
whether these genes are activated by the transcrip- 
tion factors. 
Dr. Nathans is also University Professor of Mo- 
lecular Biology and Genetics at the fohns Hopkins 
University School of Medicine. 
Books and Chapters of Books 
Lau, L.F. , and Nathans, D. 1991. Genes induced by 
serum growth factors. In Molecular Aspects of 
Cellular Regulation (Cohen, P., and Foulkes, 
J.G., Eds.). Amsterdam: Elsevier Science, vol 6, pp 
257-293. 
Nathans, D., Christy, B.A., DuBois, R., Lanahan, 
A., Sanders, L.K., and Nakabeppu, Y. 1991. 
Transcription factors induced by growth-signal- 
ing agents. In Origins of Human Cancer: A Com- 
prehensive Review (Brugge, J., Curran, T., Har- 
low, E., and McCormick, Eds.). Plainview, NY: 
Cold Spring Harbor, pp 353-364. 
Articles 
Chevray, P.M., and Nathans, D. 1992. Protein in- 
teraction cloning in yeast: identification of mam- 
malian proteins that react with the leucine zipper 
of Jun. Proc Natl Acad Sci USA 89:5789-5793. 
Murphy, T.H., Worley, P.F., Nakabeppu, Y., 
Christy, B., Gastel, J., and Baraban, J.M. 1991. 
Synaptic regulation of immediate early gene ex- 
pression in primary cultures of cortical neurons./ 
Neurochem 57:1862-1872. 
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