Insulin-induced gene 1 (INSIG1) inhibits HIV-1 production by degrading Gag via activity of the ubiquitin ligase TRC8.
You ZhangJing LuJing MaXinqi LiuPublished in: The Journal of biological chemistry (2018)
Insulin-induced gene 1 (INSIG1) regulates sterol synthesis by mediating the activation of sterol regulatory element-binding protein (SREBP) and the degradation of the HMG-CoA reductase (HMGCR). INSIG1 is up-regulated during HIV-1 infection, but its role in HIV-1 infection is unknown. In this report, using pseudovirus production, protein overexpression, and gene knockouts, we found that INSIG1 inhibits HIV-1 production by accelerating the degradation of the HIV-1 Gag protein. Unlike the degradation of HMGCR via the E3 ubiquitin ligase autocrine motility factor receptor (AMFR), a process that depends on the proteasome, INSIG1 coordinated with another ligase, translocation in renal carcinoma chromosome 8 (TRC8), and promoted Gag degradation through the lysosome pathway. We conclude that INSIG1 functions as a sentinel responsive to HIV-1 production and inhibits HIV-1 replication by degrading Gag, a process occurring at intracellular membrane sites such as the endoplasmic reticulum and endosomes where both INSIG1 and Gag may be located.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hiv aids
- hepatitis c virus
- binding protein
- men who have sex with men
- type diabetes
- copy number
- transcription factor
- high glucose
- cell proliferation
- genome wide identification
- small molecule
- glycemic control
- oxidative stress
- gene expression
- skeletal muscle
- amino acid
- biofilm formation
- fluorescent probe
- adipose tissue
- candida albicans
- cancer therapy