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Notably, mutating the nuclear localization signal (NLS: 640PKLKRQ646) of CUL5 (e.g., K642G/K644G mutations) significantly diminishes its nuclear translocation, impairing its ability to suppress cell proliferation ( CUL5 also suppresses endothelial cell proliferation and angiogenesis by promoting the degradation of Visfatin (NAMPT), thereby inhibiting MAPK/PI3K-AKT signaling (140)

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Together these results suggested that this antiretroviral therapy compromises the BBB and could be associated with HIV-1 neurological diseases