mic inhibitor of NF-/cB that prevents nuclear translo- 
cation of NF-/cB, some forms of I/cB have been found 
in the nucleus. 
Given that some other proteins with notch-like 
repeats are transcription factors, Dr. Taub wondered 
whether a nuclear form of I/cBa could itself be a 
transcriptional activator. The group found that 
Gal4-I/cBa fusions strongly transactivate a Gal4 site- 
containing promoter in 3T3 fibroblasts. The kBa 
domain responsible for this transactivation is not the 
acidic domain of kBa, but the notch-like repeat do- 
main that has been implicated in the formation of 
protein-protein interactions. 
The subcellular localization of overexpressed 
IxBa was found to be predominantly cytoplasmic 
in serum-deprived cells and nuclear in serum- 
stimulated cells. Thus I/cBa appears to have the 
capacity to enter the nucleus under some cellular 
conditions. Using double antibody immunoprecipi- 
tations. Dr. Taub and her colleagues found that cel- 
lular I/cBa in proliferating cells is associated with 
p65 NF-/cB in the cytoplasm of cells. However, when 
fused to the Gal4 DNA-binding domain, some I/cBa 
translocates to the nucleus while associated with 
p65 NF-/cB, thus accounting for its ability to transac- 
tivate the Gal 4 promoter. 
Like iKBa, several members of the NF-kB and rel 
family of transcription factors are immediate-early 
genes in regenerating liver and mitogen-treated 
cells. Dr. Taub and her colleagues examined 
changes in /cB site-binding activity during liver re- 
generation and discovered a rapidly induced, /cB 
site-binding complex, which was designated PHF 
(posthepatectomy factor). PHF is induced over 
1,000-fold within minutes posthepatectomy in a 
protein synthesis-independent manner, with peak 
activity at 30 min, and is not induced by sham 
operation. 
Although the relationship of PHF to other /cB site- 
binding proteins has not been completely character- 
ized, a change in mobility of PHF complexes be- 
tween 30 min and 3 h posthepatectomy suggests 
that the composition of the complexes changes. 
Early PHF complexes do not interact strongly with 
anti-p50 NF-kB antibodies, but PHF complexes pres- 
ent later (3-5 h posthepatectomy) react strongly, 
suggesting that they contain a p50 NF-kB subunit. 
Because PHF is induced immediately posthepa- 
tectomy in the absence of de novo protein synthesis, 
it could have a role in the regulation of immediate- 
early genes in regenerating liver. 
Dr. Taub is also Associate Professor of Genet- 
ics and Medicine at the University of Pennsyl- 
vania School of Medicine. 
Articles 
Abrams, C.S., Ruggeri, Z.M., Taub, R., Hoxie, J.A., 
Nagaswami, C, Weisel, J.W., and Shattil, S.J. 
1992. Anti-idiotypic antibodies against an anti- 
body to the platelet glycoprotein (GP) Ilb-IIIa 
complex mimic GP Ilb-Illa by recognizing fibrin- 
ogen. /S/o/ Chem 267:2775-2785. 
Taub, R., Hsu, J.-C., Garsky, V.M., Hill, B.L., Er- 
langer, B.F., and Kohn, L.D. 1992. Peptide se- 
quences from the hypervariable regions of two 
monoclonal anti-idiotypic antibodies against the 
thyrotropin (TSH) receptor are similar to TSH and 
inhibit TSH-increased cAMP production in FRTL-5 
thyroid cells, f Biol Chem 267:5977-5984. 
Tewari, M., Dobrzanski, P., Mohn, K.L., Cressman, 
D.E., Hsu, J.-C., Bravo, R., and Taub, R. 1992. 
Rapid induction in regenerating liver of RL/lF-1 
(an I/cB that inhibits NF-/cB, RelB-p50, and c-Rel- 
p50) and PHF, a novel /cB site-binding complex. 
Mol Cell Biol 12:2898-2908. 
Tewari, M., Mohn, K.L., Yue, F.E., and Taub, R. 
1992. Sequence of ratRL/lF-1 encoding I/cB iS-like 
activity and comparison with related proteins 
containing notch-like repeats. Nucleic Acids Res 
20:607. 
THE MOLECULAR BASIS OF METAMORPHOSIS IN DROSOPHILA 
CarlS. Thummel, Ph.D., Assistant Investigator 
Pulses of the steroid hormone ecdysone trigger 
the major postembryonic transitions during the de- 
velopment of the fruit fly Drosophila melanogas- 
ter. The most dramatic of these transformations oc- 
curs at the end of larval development, when a 
high-titer pulse of ecdysone signals the onset of ter- 
minal differentiation into the adult fly. This meta- 
morphosis is accompanied by dramatic changes in 
gene expression that can be visualized as changes in 
the puffing patterns of the giant salivary gland poly- 
tene chromosomes. Less than 10 "early" puffs form 
rapidly in direct response to ecdysone. As shown by 
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