CHIP/STUB1 suppresses the transcription and latent reactivation of HIV-1 via the TRAF6-NF-κB-HIV-LTR axis.

ABSTRACT: HIV-1 replication, transcription and latency are correlated with the activation of NF-κB signaling. C-terminus of Hsc70-interacting protein (CHIP or STUB1), a cellular E3 ligase, has been reported to inhibit Tat-mediated HIV-1 LTR promoter activity by degrading Tat. In this study, we demonstrated that CHIP modulates HIV infection by limiting viral transcription through an uncharacterized mechanism involving the negative regulation of TRAF6-NF-κB signaling. Mechanistically, CHIP targets the NF-κB signaling transducer TRAF6 but not TRAF2 or p65 for degradation via the ubiquitin-proteasome pathway, leading to the inhibition of TRAF6-mediated NF-κB signaling, which in turn suppresses NF-κB-dependent HIV-1 LTR transcription. Notably, in addition to the U-box domain, which is well known for prot

SUBMITTER: Zheng WH 

PROVIDER: S-EPMC12617934 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature