SAM Domain and HD Domain 1 Proteine (SAMHD1)

Human SAM Domain and HD Domain 1 (SAMHD1) Interaktionspartner

1. the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3' untranslated region of Foxp3 and Helios mRNAs in long-term culture.

2. Study identified that PIM1 and PIM3 phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1 and revealed a regulatory mechanism of virus-host interaction that governs viral escape from an intrinsic cellular immune defense via the post-translational modification of viral protein.

3. we have shown that low-level SAMHD1 expression in AML blasts at diagnosis identifies a sizeable patient subset with favorable EFS and OS upon treatment with HDAC-containing consolidation regimens.

4. This finding identifies the Endogenous reverse transcription step as an additional step of HIV-1 replication cycle that SAMHD1 restricts in nondividing myeloid target cells.

5. cyclin E2 participates in regulating viral replication through the CDK2/SAMHD1 phosphorylation pathway in an HBV infection system.

6. the state of type I IFN induction and response to, in SAMHD1 knockout (KO) human monocytic cells, was examined.

7. findings suggest that accessory protein-mediated proteosomal degradation of SAMHD1 did not exist among the ancestral non-primate lentiviruses and was uniquely gained by some primate lentiviruses after their transmission to primate species.

8. SAMHD1 activation is the predominant mechanism of HIV-1 restriction induced by type I, type II, and type III IFN signaling in macrophages.

9. 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.

10. 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.

11. SAMHD1 is not localized in dot-like structures under DNA double-strand break induction in HeLa cells.

12. 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.

13. 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.

14. 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

15. Low SAMHD1 expression is associated with HIV-1 infection.

16. Multiple domains of SAMHD1(e.g., N-terminus, nuclear localization signal, linker, HD domain, and C-terminus)are essential for Vpx-induced degradation.[review]

17. 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.

18. 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

19. Immune activation during HIV-1 infection influences SAMHD1 expression and degradation.

20. 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.

Zebrafish SAM Domain and HD Domain 1 (SAMHD1) Interaktionspartner

1. Data suggest that zebrafish may represent a system for studying the relationship between type I interferon (IFN) signaling and a loss of deoxynucleoside triphosphate triphosphohydrolase SAMHD1 activity.

Mouse (Murine) SAM Domain and HD Domain 1 (SAMHD1) Interaktionspartner

1. SAMHD1 inhibits NF-kappaB activation by interacting with NF-kappaB1/2 and reducing phosphorylation of the NF-kappaB inhibitory protein IkappaBalpha. SAMHD1 also interacts with the inhibitor-kappaB kinase epsilon (IKKepsilon) and IFN regulatory factor 7 (IRF7), leading to the suppression of the IFN-I induction pathway by reducing IKKepsilon-mediated IRF7 phosphorylation. SAMHD1 down-regulates innate immune responses to ...

2. SAMHD1's restriction of dNTP supply enhances AID's mutagenicity and that the evolution of Ig hypermutation included the repurposing of antiviral mechanisms based on dNTP starvation.

3. SAMHD1 crystal structure delineates the SAMHD1 allosteric activation process that governs SAMHD1 enzymatic activities.

4. provide genetic evidence that cell-autonomous control of lentivirus infection in myeloid cells by SAMHD1 limits virus-induced production of interferons and the induction of co-stimulatory markers

5. These data support a model in which SAMHD1 catalytic activity is regulated through tetramer stabilization by the carboxyl-terminal tail, phosphorylation destabilizing the complexes and inactivating the enzyme. ISF2 may serve to reduce the dNTP pool to very low levels as a means of restricting virus replication.

6. These observations suggest that heterozygous cancer-associated SAMHD1 mutations increase mutation rates in cancer cells.

7. SAMHD1 in the mouse blocks retroviral infection at the level of reverse transcription and is regulated through cell cycle-dependent phosphorylation.

8. phosphorylation of mSAMHD1 at T634 by CDK1/2 negatively regulates its HIV-1 restriction in differentiated cells, but does not affect its murine leukemia virus restriction in dividing cells.

9. SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells.

10. Allosteric regulation by dATP and dTTP works similarly in human and mouse SAMHD1.

11. SAMHD1 decreases dNTP pool in murine cells, restricts retroviral replication and regulates type I IFN production.

12. SAMHD1 can restrict lentiviruses in vivo and that nucleotide starvation is an evolutionarily conserved antiviral mechanism.

13. there are several Vpx residues required for SAMHD1 degradation

14. Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication