ArticleBiomolecules2026
p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages.
Article in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sulforaphane (SFN), a natural compound found in cruciferous vegetables, mobilizes the transcription factor NRF2 to protect macrophages from HIV-1. SFN/NRF2 exerts this protective effect by promoting the reduced phosphorylation of the antiviral protein SAMHD1. Phosphorylation at threonine 592 (T592) potently inhibits the capacity of SAMHD1 to restrict HIV-1. How SFN, and other NRF2 mobilizers reduce SAMHD1 T592 phosphorylation is unclear. p21 (CDKN1A) is an NRF2-responsive protein that accumulates in primary macrophages after SFN treatment. p21 blocks SAMHD1 T592 phosphorylation through the inhibition of several cyclin-dependent kinases. We therefore hypothesized that SFN acts through p21 to reduce SAMHD1 T592 phosphorylation in macrophages. Here, we use RNAi, CRISPR-Cas9, and pharmacological inhibition to deplete or delete p21 in macrophages and demonstrate that p21 is necessary for SFN to efficiently reduce SAMHD1 T592 phosphorylation and restrict HIV-1 transduction.
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