Adenovirus early region 1B 55kDa protein (E1B-55K)

The Adenovirus early region 1B 55kDa (E1B-55K) protein is a multifunctional viral regulatory protein essential for efficient adenovirus replication and host cell transformation (UniProt P03243). Its primary biological function involves the neutralization of the host's innate antiviral responses, most notably through the direct binding and inactivation of the tumor suppressor protein p53 (PubMed: 10591211). By inhibiting p53-mediated apoptosis and cell cycle arrest, E1B-55K ensures the survival of the infected cell during the viral production phase. Furthermore, E1B-55K works in conjunction with the viral E4orf6 protein to form an E3 ubiquitin ligase complex that targets various host proteins, such as Mre11 and DNA ligase IV, for degradation (PubMed: 15542591). This complex also facilitates the selective transport of viral late mRNAs from the nucleus to the cytoplasm. In oncology, E1B-55K is a pivotal target for the design of oncolytic viruses, such as ONYX-015 and H101 (Oncorine). These therapeutic agents are engineered with a deletion in the E1B-55K gene, theoretically restricting their replication to p53-deficient cancer cells while sparing normal cells where functional p53 can restrict viral growth (Wikipedia: ONYX-015).

Other names

E1B-55KAdenovirus type 5 E1B 55kDa proteinEarly adaptive protein E1B 55kDap53-associated protein

Selective oncolytic viral replication in p53-deficient cells achieved through the deletion of the E1B-55K gene, which prevents the virus from neutralizing p53 in normal cells.