Adenovirus E1A binding to DCAF10 targets proteasomal degradation of RUVBL1/2 AAA+ ATPases required for quaternary assembly of multiprotein machines, innate immunity, and responses to metabolic stress.
Nathan R ZemkeEmily HsuWilliam D BarshopJihui ShaJames A WohlschlegelArnold J BerkPublished in: Journal of virology (2023)
Inactivation of EP300/CREBB paralogous cellular lysine acetyltransferases (KATs) during the early phase of infection is a consistent feature of DNA viruses. The cell responds by stabilizing transcription factor IRF3 which activates transcription of scores of interferon-stimulated genes (ISGs), inhibiting viral replication. Human respiratory adenoviruses counter this by assembling a CUL4-based ubiquitin ligase complex that polyubiquitinylates RUVBL1 and 2 inducing their proteasomal degradation. This inhibits accumulation of active IRF3 and the expression of anti-viral ISGs, allowing replication of the respiratory HAdVs in the face of inhibition of EP300/CBEBBP KAT activity by the N-terminal region of E1A.
Keyphrases
- amino acid
- transcription factor
- dendritic cells
- sars cov
- endothelial cells
- poor prognosis
- genome wide identification
- single cell
- machine learning
- cell therapy
- circulating tumor
- respiratory tract
- signaling pathway
- induced pluripotent stem cells
- genome wide
- deep learning
- dna binding
- single molecule
- immune response
- pluripotent stem cells
- stem cells
- gene expression
- gene therapy
- stress induced
- bioinformatics analysis
- heat stress
- circulating tumor cells