Adenovirus as a Model for Oncogenesis and Control of Gene Expression 
trol region. In the absence of ElA protein, YY-1 
represses P5 transcription. In its presence the re- 
pression is relieved, and the control region be- 
comes transcriptionally active. 
To study the YY-1 factor, we prepared some 
from cultured human cells and obtained a short 
amitib acid sequence from the purified protein. 
This sequence was used to design a short probe 
DNA, which enabled us to identify and isolate a 
cDNA clone encoding the protein. Protein was 
expressed from the clone and shown to bind spe- 
cifically to the YY-1 recognition site. Sequence 
analysis of the clone revealed that YY-1 is a 68- 
kDa protein with a zinc finger DNA-binding 
motif. 
We are presently studying the mechanisms by 
which YY- 1 represses transcription and by which 
the adenovirus ElA protein relieves the repres- 
sion. We also wish to determine whether ElA 
protein mediates its effects on the positive-acting 
AP- 1 and the negative-acting YY- 1 factors through 
the same or different mechanisms. That is, does 
the ElA protein mediate just one biochemical re- 
action that affects AP-1 and YY-1 differently, or 
does it carry out multiple, physiologically dis- 
tinct biochemical processes? 
In addition to the ElA protein, which functions 
to induce transcription, we have studied the ade- 
novirus 55-kDa protein induced by ElB. This 
protein also controls the accumulation of 
mRNAs, but it acts after transcription. It simulta- 
neously blocks the accumulation of cellular 
mRNAs and enhances accumulation of viral 
mRNAs. Further studies indicated that the pro- 
tein's discrimination of viral from cellular 
mRNAs is based on the site of synthesis. If an RNA 
is transcribed from the viral chromosome, its ac- 
cumulation is enhanced; if it is transcribed from a 
cellular chromosome, its accumulation is 
blocked. 
We determined the localization of the ElB 55- 
kDa protein within the infected cell, using a tech- 
nique termed immunogold electron microscopy. 
The protein was localized to the periphery of 
spherical bodies previously shown to be sites of 
viral DNA replication and transcription. 
Localization of the ElB protein at the replica- 
tion-transcription centers is consistent with its 
ability to enhance accumulation of viral mRNAs. 
Its location makes it available to these mRNAs 
shortly after their synthesis and processing. But 
how does this localization prevent cytoplasmic 
accumulation of host cell mRNAs? It seems likely 
that the protein interacts with and draws to 
the periphery of viral replication-transcription 
centers a cellular factor that functions to move 
mRNAs from their site of synthesis and processing 
to the nuclear pore for transport out of the nu- 
cleus. Relocation of a cellular factor required for 
intranuclear movement of RNAs could explain 
how the ElB protein can inhibit accumulation of 
RNAs transcribed from cellular locations and si- 
multaneously stimulate accumulation of tran- 
scripts derived from the viral chromosome. We 
are presently searching for cellular factors that 
interact with this protein. 
404 
