Adenovirus E4 open reading frame 1 protein (E4orf1)

Adenovirus E4 open reading frame 1 protein (E4orf1) is a small viral protein encoded by the E4 region of the adenovirus genome (UniProt). It plays a critical role in viral replication and cellular signaling by interacting with PDZ-domain-containing proteins, such as DLG1, to activate the Phosphoinositide 3-kinase (PI3K) pathway (PubMed: 21832151). This activation occurs independently of the insulin receptor, leading to increased glucose uptake in peripheral tissues and reduced glucose production in the liver (PubMed: 25213335). While E4orf1 from certain serotypes like Ad9 is recognized as an oncoprotein capable of inducing tumors, the E4orf1 from Ad36 has gained significant interest for its potential to improve glycemic control in metabolic disorders (PubMed: 22411024). Consequently, it is being investigated as a novel therapeutic template for treating Type 2 Diabetes and obesity, though its oncogenic risks remain a primary safety concern for clinical application (PubMed: 28844881).

Other names

E4-ORF1Early region 4 open reading frame 1 proteinAd36 E4orf1Ad9 E4orf1

Activates the PI3K/Akt signaling pathway by binding to PDZ-domain-containing proteins, thereby promoting glucose transporter (GLUT) translocation to the cell membrane independently of insulin receptor activation (PubMed: 21832151).