teins, VP16 triggers activation of gene expression by 
use of a highly acidic segment of 60 amino acids lo- 
cated at its carboxyl terminus. The mechanism by 
which this acidic domain activates transcription is 
unknown. 
B. Derivation of a trans-dominant form of VP16. 
During the course of molecular genetic character- 
ization of VP16, Dr. Steven Triezenberg and Dr. Mc- 
Knight observed that truncated forms of the pro- 
tein lacking the acidic activation domain impede 
the function of normal VP16. Dr. Alan Friedman 
and Dr. McKnight extended these observations by 
preparing a cell line that constitutively expresses an 
activation-defective form of VP16. The truncated 
VP16 is located in the nucleus of these cells. These 
PUBLICATIONS 
cells exhibit substantial immunity when challenged 
by infecting HSV. The cause of the observed immu- 
nity has been traced to an impediment in the acti- 
vation of IE genes. Drs. Friedman and McKnight, in 
collaboration with Dr. Edward Birkenmeier of the 
Jackson Laboratory, recently succeeded in generat- 
ing a transgenic mouse that expresses the trun- 
cated form of VP16. Experiments are under way to 
test whether such procedures have rendered the 
transgenic mice immune to HSV infection. 
Dr. McKnight is also a staff member of the De- 
partment of Embryology at The Carnegie Institu- 
tion of Washington and Adjunct Professor in the 
Departments of Biology and of Molecular Genetics 
at The Johns Hopkins University. 
Articles 
Birkenmeier, E.H., Gwynn, B., Howard, S., Jerry, J., Gordon, J. I., Landschulz, WH., and McKnight, S.L. 1989. 
Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding 
CCAAT/enhancer binding protein. Genes Dev 3:1146-1156. 
Friedman, A.D., Triezenberg, S.J., and McKnight, S.L. 1988. Expression of a truncated viral ?ran5-activator se- 
lectively impedes lytic infection by its cognate virus. Nature 335:452-454. 
Johnson, P.F., and McKnight, S.L. 1989. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem 
58:799-839. 
Landschulz, WH., Johnson, PF., and McKnight, S.L. 1988. The leucine zipper: a hypothetical structure com- 
mon to a new class of DNA binding proteins. Science 240:1759-1764. 
Landschulz, WH., Johnson, PR, and McKnight, S.L. 1989. The DNA binding domain of the rat liver nuclear 
protein C/EBP is bipartite. Science 243:1681-1688. 
Triezenberg, S.J., Kingsbury, R.C. , and McKnight, S.L. 1988. Functional dissection of VP16, the fmns-activator 
of herpes simplex virus immediate early gene expression. Genes Dev 2:718-729. 
Triezenberg, SJ., LaMarco, K.L., and McKnight, S.L. 1988. Evidence of DNA:protein interactions that mediate 
HSV-1 immediate early gene activation by VP16. Genes Dev 2:730-742. 
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