Differential dysregulation of β-TrCP1 and -2 by HIV-1 Vpu leads to inhibition of canonical and non-canonical NF-κB pathways in infected cells.

ABSTRACT: The HIV-1 Vpu protein is expressed late in the virus lifecycle to promote infectious virus production and avoid innate and adaptive immunity. This includes the inhibition of the NF-κB pathway which, when activated, leads to the induction of inflammatory responses and the promotion of antiviral immunity. Here we demonstrate that Vpu can inhibit both canonical and non-canonical NF-κB pathways, through the direct inhibition of the F-box protein β-TrCP, the substrate recognition portion of the Skp1-Cul1-F-box (SCF)^β-TrCP ubiquitin ligase complex. There are two paralogues of β-TrCP (β-TrCP1/BTRC and β-TrCP2/FBXW11), encoded on different chromosomes, which appear to be functionally redundant. Vpu, however, is one of the few β-TrCP substrates to differentiate between the two paralogues

SUBMITTER: Pickering S 

PROVIDER: S-EPMC10470808 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature