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Data show that SAM Domain and HD Domain-Containing Protein 1 (SAMHD1) is specifically targeted by protein phosphatase 2 regulatory subunit Balpha protein (PP2A-B55alpha) holoenzymes during mitotic exit.
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SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases.
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SAMHD1 is not localized in dot-like structures under DNA double-strand break induction in HeLa cells.
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study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.
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Compared with control cells, infection of SAMHD1-silenced human monocytic cells or primary macrophages with Sendai virus or HIV-1, or treatment with inflammatory stimuli, induces significantly higher levels of NF-kappaB activation and IFN-I induction. SAMHD1 down-regulates innate immune responses to viral infections and inflammatory stimuli.
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SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks
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Low SAMHD1 expression is associated with HIV-1 infection.
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Multiple domains of SAMHD1(e.g., N-terminus, nuclear localization signal, linker, HD domain, and C-terminus)are essential for Vpx-induced degradation.[review]
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findings indicate a novel role for SAMHD1 in regulating HIV-1 latency, which enhances our understanding of the mechanisms regulating proviral gene expression in CD4(+) T cells.
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results demonstrate that the interaction of CD81 with SAMHD1 controls the metabolic rate of HIV-1 replication by tuning the availability of building blocks for reverse transcription, namely dNTPs
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Immune activation during HIV-1 infection influences SAMHD1 expression and degradation.
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Studies of the phosphomimetic and tetramerization-defective mutants of SAMHD1 reveal poor correlation between tetramerization propensity and dNTPase activity observed in vitro and the ability of the proteins to deplete cellular dNTPs and to restrict retroviral restriction. These results suggest that enzymatic activity of SAMHD1 may be subject to additional cellular regulatory mechanisms that have not yet been elucidated.
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Upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3.
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Findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.
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These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of reverse transcription (RT)that acts independently of dNTP concentrations and is specific to resting CD4 T cells.
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results indicate that the RXL motif is critical for tetramer formation, dNTPase activity, and HIV-1 restriction. These findings help us understand SAMHD1 interactions with other host proteins and the mechanisms regulating SAMHD1 structure and functions in cells.
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These results suggest that SAMHD1 is a relevant restriction factor for HBV and restricts reverse transcription through its dNTPase activity
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SAMHD1 may constitute a promising target to improve a wide range of therapies for both hematological and non-haematological malignancies.
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Study demonstrates a consistent resistance profile to PARPi and a unique cross-resistance profile to non-PARPi drugs in different PARPi-resistant U251 glioblastoma cells and reveals 53BP1 loss and SAMHD1 overexpression as the primary mechanisms responsible for their resistance to PARPi and Ara-C, respectively.
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Study identify three critical cysteine residues of SAMHD1 (Cys341, Cys350, and Cys522) that create a ''redox switch'' through the formation of intrachain disulfide bonds to reversibly inhibit SAMHD1 tetramerization and dNTPase activity. SAMHD1 is oxidized in cells in response to proliferative signals and colocalizes with sites of protein oxidation outside of the nucleus.
