[Frontiers in Bioscience 7, d407-413, Feburary 1, 2002]

ADENOVIRAL E1A: EVERLASTING TOOL, VERSATILE APPLICATIONS, CONTINUOUS CONTRIBUTIONS AND NEW HYPOTHESES

Nianli Sang1, Jaime Caro1 and Antonio Giordano2

1Cardeza Foundation for Hematological Research, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, 2Department of Anatomy, Pathology and Cell Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Adenoviral E1A, a tool to identify regulatory proteins
4. Targeting SWI/SNF: modulating chromatin structure
5. E1A-mediated transactivation
6. E1A-mediated transcriptional repression
7. E1A-mediated apoptosis and sensitization
8. E1A-mediated tumor suppression and gene therapy
9. Perspective
10. Acknowledgements
11. References

1. ABSTRACT

Adenoviral E1A is an indispensable protein for virus-host interaction. To provide a suitable environment for viral replication, E1A physically interacts with multiple cellular proteins to reprogram gene expression and other processes of the host cells. Proteins targeted by E1A include the pRb family of pocket proteins, p300/CBP, cyclin/Cdk, the carboxyl terminal binding protein (CtBP), transcriptional regulator YY1, and the recently identified RACK1 and SWI/SNF complex. Reprogramming activity of E1A and the host cell response to this reprogramming lead to transformation, growth arrest or apoptosis. Based on the ability of E1A to override the fundamental controls of host cells, E1A has been being utilized to make continuous contributions not only to a better understanding of the molecular mechanisms underlying the regulation of transcription, cell division, apoptosis and tumorigenesis but also to new therapeutics such as gene therapy.