Adenovirus E1B protein usually refers to one of two proteins transcribed from the E1B gene of the adenovirus: a 55kDa protein and a 19kDa protein. These two proteins are needed to block apoptosis in adenovirus-infected cells. E1B proteins work to prevent apoptosis that is induced by the small adenovirus E1A protein, which stabilizes p53, a tumor suppressor.[1][2]
Functions
E1B-19k
E1B-19k blocks a p53-independent apoptosis mechanism. Without E1B-19k, degradation of both cellular and viral DNA occurs, in addition to premature host cell death during the lytic cycle, thus limiting viral replication.[3]E1B-19k mimics MCL1, which is a cellular antiapoptotic protein.[4] In infected cells, the expression of E1A results in the degradation of MCL-1, which normally binds the propaptotic protein, BAK.[4] BAK activation induces apoptosis by cooligomerizing with another proapoptotic protein, BAX. Together, BAK and BAX form pores in the mitochondrial membrane, releasing apoptogenic proteins like cytochrome c.[3][5] This and other proteins released from the mitochondria lead to activation of caspase-9 and caspase-3 and the resulting apoptotic program.[6] However, in adenovirus-infected cells, activated BAK and BAX are sequestered by E1B-19k, preventing the pathway.[3]
E1B-55k
E1B-55k blocks p53 from inhibiting cell cycling and stops it from inducing apoptosis.[7] Observations show that E1b-55k inhibits activation by p53 by binding a repression domain to it, converting it from an activator to a repressor of p53-activated genes. This stabilizes p53 and causes a large increase in p53 concentration. Additionally, p53 bound to E1B-55k has an affinity for its binding site that is ten times higher than free p53.[8] Presumably, this increased affinity and concentration of p53 turns the p53-E1B-55k complex into a powerful repressor.[9]
E1B-55k also forms a complex with E4orf6, a viral protein.[10] The E1B-55k/E4orf6 complex in infected cells assembles with other cellular proteins to form a ubiquitin ligase complex.[11] Essentially, the E1B-55k/E4orf6 complex takes over the cellular ubiquitin ligase complexes and gives them viral substrate-recognition subunits.[9] There are two known substrates for this ubiquitin ligases; p53 and the MRN complex.[11][12] The MRN complex, if not bound by the E1B-55K/E4orf6 ubiquitin ligase, will treat the ends of the viral DNA like a double-stranded DNA break and the viral DNA becomes ligated into long concatemers of randomly assorted genomes.[13]
Structural and bioinformatics studies have shown that E1B-55k, which is specific to mammalian mastadenoviruses, has evolved by exaptation from an LH3-like minor capsid protein encoded by atadenoviruses.[14]