E1B55k

E1B55k is a viral regulatory protein encoded by the E1B region of many human adenoviruses, most notably adenovirus type 5. The protein has a molecular mass of approximately 55 kilodaltons and functions as a multifunctional modulator of the host cell that supports viral replication and gene expression.

A central role of E1B55k is the suppression of host defenses, particularly the p53 tumor suppressor pathway. E1B55k binds to p53 and, in conjunction with other viral proteins such as E4orf6, promotes the degradation and functional inactivation of p53. This helps prevent p53-dependent apoptosis and cell cycle arrest, creating a cellular environment more conducive to viral replication. E1B55k also contributes to the export and processing of viral late mRNAs and can influence host transcription and RNA processing.

In combination with E4orf6, E1B55k forms a Cullin5-based E3 ubiquitin ligase complex that ubiquitinates p53 and other substrates, targeting them for proteasomal degradation. This complex is also implicated in modulating DNA damage response pathways by targeting components of the MRN complex, among others, thereby reducing antiviral signaling and promoting viral genome replication.

E1B55k has been a focus in the study of virus–host interactions and in the development of oncolytic adenoviruses. Deletion of E1B55k in early oncolytic constructs (for example, ONYX-015) was intended to restrict viral replication to p53-deficient tumors, though subsequent work revealed that tumor selectivity depends on multiple factors beyond p53 status.

Across adenovirus serotypes, E1B55k is considered essential for efficient replication and for modulating host defenses, reflecting its status as a key regulator of the viral life cycle.