SAM Domain and HD Domain 1 Proteine (SAMHD1)

Human SAM Domain and HD Domain 1 (SAMHD1) Interaktionspartner

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

2. 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.

3. Compared with control cel (zeige NFKB1 Proteine)ls, infection of SAMHD1-silenced human mon (zeige NFKB1 Proteine)ocytic cells or primary macrophages with Sendai (zeige NFKB1 Proteine)virus or HIV-1, or treatment wit (zeige NFKBIA Proteine)h inflammatory stimuli, induces significantly higher levels of NF-kappaB act (zeige IKBKE Proteine)ivation and IFN-I induction. SAMHD1 (zeige IRF7 Proteine) down-regulates innate immune responses to viral infections and inflammatory stimul (zeige IKBKE Proteine)i.

4. 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

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

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

7. 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 (zeige CD4 Proteine)(+) T cells.

8. results demonstrate that the interaction of CD81 (zeige CD81 Proteine) with SAMHD1 controls the metabolic rate of HIV-1 replication by tuning the availability of building blocks for reverse transcription, namely dNTPs

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

10. 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 (zeige IFNA Proteine) (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 (zeige NFKB1 Proteine) activation by interacting with NF-kappaB1 (zeige NFKB1 Proteine)/2 and reducing phosphorylation of the NF-kappaB (zeige NFKB1 Proteine) inhibitory protein IkappaBalpha (zeige NFKBIA Proteine). SAMHD1 also interacts with the inhibitor-kappaB kinase epsilon (IKKepsilon (zeige IKBKE Proteine)) and IFN regulatory factor 7 (IRF7 (zeige IRF7 Proteine)), leading to the suppression of the IFN-I induction pathway by reducing IKKepsilon (zeige IKBKE Proteine)-mediated IRF7 (zeige IRF7 Proteine) 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 (zeige CDK1 Proteine)/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 (zeige IFNA Proteine) production in mouse myeloid cells.

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