Adenoviral E1A oncoprotein: The Butterfly Effect

Abstract

Viral infections are one of the leading causes of death in humans and are usually caused by the adenovirus. The early region protein (E1A) is a multifunctional protein expressed by the adenovirus and essential for transformation of the host cell, ultimately resulting in oncogenesis. Through E1A's interactions with the host cell's retinoblastoma protein (pRb) and CREB binding protein (CBP), E1A prevents natural cellular functions. Our focus is the interaction site between E1A and CBP/p300, specifically the transcriptional adaptor zinc finger‐2 (TAZ2) of CBP/p300. Upon interaction with the TAZ2 domain, E1A undergoes coupled folding, allowing it to bind with TAZ2, competing with, and inactivating, the transactivation domain (TAD) of the tumor suppressor p53. Through competition with p53, E1A is able to inhibit apoptosis and cell cycle arrest, thus causing the cell to divide uncontrollably. E1A has the ability to reprogram gene expression. Understanding the structure of the complex will help us to design a therapeutic that would prevent E1A from interacting with CBP, allowing normal interaction with p53 to occur. This will prevent cancer in association with adenovirus infection and help us to understand more about cancer‐causing viruses in general. The El Capitan High School SMART Team (Students Modeling A Research Topic) modeled E1A using 3D printing technology. Supported by a grant from HHMI Pre‐College Program