SAMHD1

Last updated
SAMHD1
3u1n.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SAMHD1 , CHBL2, DCIP, HDDC1, MOP-5, SBBI88, SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1, hSAMHD1
External IDs OMIM: 606754 MGI: 1927468 HomoloGene: 9160 GeneCards: SAMHD1
Orthologs
SpeciesHumanMouse
Entrez

25939

56045

Ensembl

ENSG00000101347

ENSMUSG00000027639

UniProt

Q9Y3Z3

Q60710

RefSeq (mRNA)

NM_015474
NM_001363729
NM_001363733

NM_001139520
NM_018851
NM_001370610

RefSeq (protein)

NP_056289
NP_001350658
NP_001350662

NP_001132992
NP_061339
NP_001357539

Location (UCSC) Chr 20: 36.89 – 36.95 Mb Chr 2: 156.94 – 156.98 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene. SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV in dendritic cells, [5] macrophages, [6] monocytes [7] and resting CD4+ T lymphocytes. [8] It is an enzyme that exhibits phosphohydrolase activity, [9] [10] converting deoxynucleoside triphosphates (dNTPs) to inorganic phosphate (iPPP) and a 2'-deoxynucleoside (i.e. deoxynucleosides without a phosphate group). In doing so, SAMHD1 depletes the pool of dNTPs available to a reverse transcriptase for viral cDNA synthesis and thus prevents viral replication. [11] SAMHD1 has also shown nuclease activity. [12] Although a ribonuclease activity was described to be required for HIV-1 restriction, [13] recent data confirmed that SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity. [14]

Nomenclature

The SAMHD1 protein is also known as:

Gene

The gene encoding human SAMHD1 was originally identified in a human dendritic cell cDNA library as an orthologue of a mouse gene IFN-γ-induced gene Mg11. [16] The SAMHD1 gene is located on chromosome 20. SAMHD1 spans 59,532 bp of genomic sequence (chromosome 20:34,954,059–35,013,590) in 16 exons and encodes a 626 amino-acid (aa) protein with a molecular weight of 72.2 kDa. [17] [18] SAMHD1 expressed in both cycling and noncycling cells, but the antiviral activity of SAMHD1 is limited to noncycling cells. [19]

Structure

The SAMHD1 is 626 amino acids (aa) long and has 2 domains:

a. Sterile alpha motif (SAM) domain: residues 45 – 110 aa. [20] [21] In general, SAM domains are known to function as protein–protein and protein–nucleic acid interactions in organisms from yeast to humans, docking sites for kinases, signal transduction and regulation of transcription. [22] [23]

b. Histidine- Aspartic (HD) domain-containing protein 1: residues 164 – 319 aa. [20] [21] HD domains proteins are characterized by a doublet of histidine and aspartic acid catalytic residues, and have been shown to possess putative nuclease, dGTP triphosphatase, phosphatase or phosphodiesterase activities. [22] [24]

A crystal structure of a SAMHD1 fragment comprising catalytic core reveals that the protein is dimeric. [10] Also studies have shown that SAMHD1 oligomerizes and forms tetramers. [25] SAMHD1 is phosphorylated on residue T592 in cycling cells but that this phosphorylation is lost when cells are in a noncycling state. [26]

Function

Mutations in SAMHD1 are found in Aicardi–Goutières syndrome (AGS), “a hereditary autoimmune encephalopathy that is characterized by aberrant production of type I interferon (IFN) and symptoms mimicking congenital viral infection”. [21] Monocytes isolated from individuals with AGS are highly susceptible to HIV-1. [7]

SAMHD1 was identified as a host protein that is bound and blocked by lentiviral protein, Vpx. Vpx promotes macrophage and DC infection by targeting SAMHD1. [27]

The human SAMHD1 protein has dNTP triphosphatase activity, specifically dGTP-stimulated dNTP triphosphohydrolase activity, and nuclease activity against single-stranded DNA and RNA which is associated with its HD domain. [12] [28] Other studies demonstrated that silencing SAMHD1 enhanced HIV-1 and SIV Δvpx infection of myeloid cells, also enhances HIV-1 infection of resting CD4+ T cells. [19] [28]

Role in disease

Aicardi-Goutieres syndrome

16 mutations in the SAMHD1 gene have been identified in patients with Aicardi-Goutieres syndrome. Mutations result in a SAMHD1 less functional protein. However, it is not known how this protein dysfunction leads to immune system abnormalities, inflammatory damage to the brain and skin, and other characteristics of this syndrome. [7] [21]

Restriction of viral infection

SAMHD1 was identified as the cellular protein responsible of the reverse transcription block to HIV-1 infection observed in myeloid cells as well as in quiescent CD4+ T cells. SAMHD1 inhibits HIV-1 infection in myeloid cells by limiting the intracellular pool of dNTPs. [27] The dNTP triphosphohydrolase activity of SAMHD1 has been proposed to reduce the intracellular dNTP level, restricting HIV-1 replication and preventing activation of the immune system, a nuclease activity against single-stranded (ss)DNAs and RNAs, as well as against RNA in DNA/RNA hybrids. [22] [27] Retroviral restriction ability of SAMHD1 is regulated by phosphorylation, for this purpose SAMHD1 associates with the cyclin A2/CDK1 complex that mediates its phosphorylation at threonine 592. Phosphorylated SAMHD1 has been observed to have minimal to no activity in cycling cells. Conversely, unphosphorylated SAMHD1 in non-cycling cells have potent restriction activity. [26]

Expression modulation and antimetabolite degradation in cancer cells

SAMHD1 protein expression can be influenced at four levels in cancer cells. First, mutations in the SAMHD1 gene can prevent SAMHD1 mRNA generation or a functional protein after translations. [29] Second, promoter methylation can prevent SAMHD1 mRNA transcription. [30] [31] Third, miRNA-155 and miRNA-181a can prevent the translation, thus preventing protein production. [32] [33] Finally, SAMHD1 degradation occurs during the S phase of the cell cycle. [34] Non-adherent tumor cell lines – B cells, T cells and myeloid cells can be rapidly dividing cells, have low to no detectable levels of SAMHD1 protein, as compared to adherent cells. Regulation of dNTP concentration by SAMHD1 in cancer cells might be an important mechanism with therapeutic implications. [35] Antimetabolites are anticancer nucleosides, nucleotides, and base analogs used as anticancer agents to promote cell death by several different mechanisms of action. [36] For some of these antimetabolites, the intracellular triphosphate form of the analog is the active compound. [36] SAMHD1 has been shown to be able to hydrolyze arabinose 5’-triphosphates. [37] SAMHD1 has been shown to be a biomarker and influence arabinose C (ara-C; cytarabine) responsiveness. [38] Viral protein x (Vpx) has been proposed to be potential therapy to improve cytarabine therapy for hematological malignancies. [39]

Related Research Articles

HIV Human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.

A restriction enzyme, restriction endonuclease, or restrictase is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class of the broader endonuclease group of enzymes. Restriction enzymes are commonly classified into five types, which differ in their structure and whether they cut their DNA substrate at their recognition site, or if the recognition and cleavage sites are separate from one another. To cut DNA, all restriction enzymes make two incisions, once through each sugar-phosphate backbone of the DNA double helix.

Ribonuclease H Enzyme family

Ribonuclease H is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes.

Cytarabine Chemical compound (chemotherapy medication)

Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by injection into a vein, under the skin, or into the cerebrospinal fluid. There is a liposomal formulation for which there is tentative evidence of better outcomes in lymphoma involving the meninges.

A nucleoside triphosphate is a molecule containing a nitrogenous base bound to a 5-carbon sugar, with three phosphate groups bound to the sugar. It is an example of a nucleotide. They are the molecular precursors of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways.

Clofarabine

Clofarabine is a purine nucleoside antimetabolite marketed in the United States and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating relapsed or refractory acute lymphoblastic leukaemia (ALL) in children after at least two other types of treatment have failed. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out. Ongoing trials are assessing its efficacy for managing other cancers.

The genome and proteins of HIV have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

RNA-dependent RNA polymerase Enzyme that synthesizes RNA from an RNA template

RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription of RNA from a DNA template.

ERCC1 Protein-coding gene in the species Homo sapiens

DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

ADAR Mammalian protein found in Homo sapiens

The double-stranded RNA-specific adenosine deaminase enzyme family are encoded by the ADAR family genes. ADAR stands for adenosine deaminase acting on RNA. This article focuses on the ADAR proteins; This article details the evolutionary history, structure, function, mechanisms and importance of all proteins within this family.

TREX1

Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.

MDA5

MDA5 is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses. It is generally believed that MDA5 recognizes double stranded RNA (dsRNA) over 2000nts in length, however it has been shown that whilst MDA5 can detect and bind to cytoplasmic dsRNA, it is also activated by a high molecular weight RNA complex composed of ssRNA and dsRNA. For many viruses, effective MDA5-mediated antiviral responses are dependent on functionally active LGP2. The signaling cascades in MDA5 is initiated via CARD domain. Some observations made in cancer cells show that MDA5 also interacts with cellular RNA is able to induce an autoinflammatory response.

USP18 Protein-coding gene in the species Homo sapiens

Ubiquitin specific peptidase 18 (USP18), also known as UBP43, is a type I interferon receptor repressor and an isopeptidase. In humans, it is encoded by the USP18 gene. USP18 is induced by the immune response to type I and III interferons, and serves as a negative regulator of type I interferon, but not type III interferon. Loss of USP18 results in increased responsiveness to type I interferons and life-threatening autoinflammatory disease in humans due to the negative regulatory function of USP18 in interferon signal transduction. Independent of this activity, USP18 is also a member of the deubiquitinating protease family of enzymes. It is known to remove ISG15 conjugates from a broad range of protein substrates, a process known as deISGylation.

RNASEH2A Protein-coding gene in the species Homo sapiens

Ribonuclease H2 subunit A, also known as RNase H2 subunit A, is an enzyme that in humans is encoded by the RNASEH2A gene.

RNASEH2B

Ribonuclease H2, subunit B is a protein that in humans is encoded by the RNASEH2B gene. RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits, and degrades the RNA of RNA:DNA hybrids. The non-catalytic B subunit of RNase H2 is thought to play a role in DNA replication.

Genome editing Type of genetic engineering

Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site specific locations.

Cas9 Microbial protein found in Streptococcus pyogenes M1 GAS

Cas9 is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.

Vpx is a virion-associated protein encoded by human immunodeficiency virus type 2 HIV-2 and most simian immunodeficiency virus (SIV) strains, but that is absent from HIV-1. It is similar in structure to the protein Vpr that is carried by SIV and HIV-2 as well as HIV-1. Vpx is one of five accessory proteins carried by lentiviruses that enhances viral replication by inhibiting host antiviral factors.

Aicardi–Goutières syndrome Medical condition

Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin. The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of in utero acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.

RNASEH2C

Ribonuclease H2 subunit C is a protein that in humans is encoded by the RNASEH2C gene. RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits, and degrades the RNA of RNA:DNA hybrids.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000101347 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027639 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Ségéral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (May 2011). "SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx". Nature. 474 (7353): 654–7. doi:10.1038/nature10117. PMC   3595993 . PMID   21613998.
  6. ↑ Hrecka K, Hao C, Gierszewska M, Swanson SK, Kesik-Brodacka M, Srivastava S, Florens L, Washburn MP, Skowronski J (June 2011). "Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein". Nature. 474 (7353): 658–61. doi:10.1038/nature10195. PMC   3179858 . PMID   21720370.
  7. 1 2 3 Berger A, Sommer AF, Zwarg J, Hamdorf M, Welzel K, Esly N, Panitz S, Reuter A, Ramos I, Jatiani A, Mulder LC, Fernandez-Sesma A, Rutsch F, Simon V, König R, Flory E (December 2011). "SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection". PLOS Pathogens. 7 (12): e1002425. doi:10.1371/journal.ppat.1002425. PMC   3234228 . PMID   22174685.
  8. ↑ Pan X, Baldauf HM, Keppler OT, Fackler OT (June 2013). "Restrictions to HIV-1 replication in resting CD4+ T lymphocytes". Cell Research. 23 (7): 876–885. doi:10.1038/cr.2013.74. PMC   3698640 . PMID   23732522.
  9. ↑ Powell RD, Holland PJ, Hollis T, Perrino FW (December 2011). "Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase". The Journal of Biological Chemistry. 286 (51): 43596–600. doi: 10.1074/jbc.C111.317628 . PMC   3243528 . PMID   22069334.
  10. 1 2 Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, Walker PA, Kelly G, Haire LF, Yap MW, de Carvalho LP, Stoye JP, Crow YJ, Taylor IA, Webb M (November 2011). "HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase". Nature. 480 (7377): 379–82. Bibcode:2011Natur.480..379G. doi:10.1038/nature10623. PMID   22056990. S2CID   205226940.
  11. ↑ Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, Bloch N, Maudet C, Bertrand M, Gramberg T, Pancino G, Priet S, Canard B, Laguette N, Benkirane M, Transy C, Landau NR, Kim B, Margottin-Goguet F (February 2012). "SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates". Nature Immunology. 13 (3): 223–8. doi:10.1038/ni.2236. PMC   3771401 . PMID   22327569.
  12. 1 2 Beloglazova N, Flick R, Tchigvintsev A, Brown G, Popovic A, Nocek B, Yakunin AF. “Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction”. Beloglazova N, Flick R, Tchigvintsev A, Brown G, Popovic A, Nocek B, Yakunin AF (March 2013). "Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction". The Journal of Biological Chemistry. 288 (12): 8101–10. doi: 10.1074/jbc.M112.431148 . PMC   3605629 . PMID   23364794.
  13. ↑ Ryoo J, Choi J, Oh C, Kim S, Seo M, Kim SY, Seo D, Kim J, White TE, Brandariz-Nuñez A, Diaz-Griffero F, Yun CH, Hollenbaugh JA, Kim B, Baek D, Ahn K (August 2014). "The ribonuclease activity of SAMHD1 is required for HIV-1 restriction". Nature Medicine. 20 (8): 936–41. doi:10.1038/nm.3626. PMC   4318684 . PMID   25038827.
  14. ↑ Antonucci JM, St Gelais C, de Silva S, Yount JS, Tang C, Ji X, Shepard C, Xiong Y, Kim B, Wu L (October 2016). "SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity". Nature Medicine. 22 (10): 1072–1074. doi:10.1038/nm.4163. PMC   5069697 . PMID   27711056.
  15. ↑ Chahwan C, Chahwan R (May 2012). "Aicardi-Goutieres syndrome: from patients to genes and beyond". Clinical Genetics. 81 (5): 413–20. doi:10.1111/j.1399-0004.2011.01825.x. PMID   22149989. S2CID   28902344.
  16. 1 2 3 Li N, Zhang W, Cao X (November 2000). "Identification of human homologue of mouse IFN-gamma induced protein from human dendritic cells". Immunology Letters. 74 (3): 221–4. doi:10.1016/S0165-2478(00)00276-5. PMID   11064105.
  17. ↑ Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, et al. (July 2009). "Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response". Nature Genetics. 41 (7): 829–32. doi:10.1038/ng.373. PMC   4154505 . PMID   19525956.
  18. ↑ Welbourn S, Miyagi E, White TE, Diaz-Griffero F, Strebel K (October 2012). "Identification and characterization of naturally occurring splice variants of SAMHD1". Retrovirology. 9: 86. doi:10.1186/1742-4690-9-86. PMC   3503569 . PMID   23092512.
  19. 1 2 Baldauf HM, Pan X, Erikson E, Schmidt S, Daddacha W, Burggraf M, Schenkova K, Ambiel I, Wabnitz G, Gramberg T, Panitz S, Flory E, Landau NR, Sertel S, Rutsch F, Lasitschka F, Kim B, König R, Fackler OT, Keppler OT (November 2012). "SAMHD1 restricts HIV-1 infection in resting CD4(+) T cells". Nature Medicine. 18 (11): 1682–7. doi:10.1038/nm.2964. PMC   3828732 . PMID   22972397.
  20. 1 2 White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen L, Kim B, Brojatsch J, Diaz-Griffero F (February 2013). "Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1". Virology. 436 (1): 81–90. doi:10.1016/j.virol.2012.10.029. PMC   3767443 . PMID   23158101.
  21. 1 2 3 4 Crow YJ, Rehwinkel J (October 2009). "Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity". Human Molecular Genetics. 18 (R2): R130-6. doi:10.1093/hmg/ddp293. PMC   2758706 . PMID   19808788.
  22. 1 2 3 Ayinde D, Casartelli N, Schwartz O (October 2012). "Restricting HIV the SAMHD1 way: through nucleotide starvation". Nature Reviews. Microbiology. 10 (10): 675–80. doi:10.1038/nrmicro2862. PMID   22926205. S2CID   24799736.
  23. ↑ Kim CA, Bowie JU (December 2003). "SAM domains: uniform structure, diversity of function". Trends in Biochemical Sciences. 28 (12): 625–8. doi:10.1016/j.tibs.2003.11.001. PMID   14659692.
  24. ↑ Aravind L, Koonin EV (December 1998). "The HD domain defines a new superfamily of metal-dependent phosphohydrolases". Trends in Biochemical Sciences. 23 (12): 469–72. doi:10.1016/s0968-0004(98)01293-6. PMID   9868367.
  25. ↑ Yan J, Kaur S, DeLucia M, Hao C, Mehrens J, Wang C, Golczak M, Palczewski K, Gronenborn AM, Ahn J, Skowronski J (April 2013). "Tetramerization of SAMHD1 is required for biological activity and inhibition of HIV infection". The Journal of Biological Chemistry. 288 (15): 10406–17. doi: 10.1074/jbc.M112.443796 . PMC   3624423 . PMID   23426366.
  26. 1 2 White TE, Brandariz-Nuñez A, Valle-Casuso JC, Amie S, Nguyen LA, Kim B, Tuzova M, Diaz-Griffero F (April 2013). "The retroviral restriction ability of SAMHD1, but not its deoxynucleotide triphosphohydrolase activity, is regulated by phosphorylation". Cell Host & Microbe. 13 (4): 441–51. doi:10.1016/j.chom.2013.03.005. PMC   3864637 . PMID   23601106.
  27. 1 2 3 Mashiba M, Collins KL (January 2013). "Molecular mechanisms of HIV immune evasion of the innate immune response in myeloid cells". Viruses. 5 (1): 1–14. doi: 10.3390/v5010001 . PMC   3564108 . PMID   23344558.
  28. 1 2 Descours B, Cribier A, Chable-Bessia C, Ayinde D, Rice G, Crow Y, Yatim A, Schwartz O, Laguette N, Benkirane M (October 2012). "SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4(+) T-cells". Retrovirology. 9: 87. doi:10.1186/1742-4690-9-87. PMC   3494655 . PMID   23092122.
  29. ↑ Clifford R, Louis T, Robbe P, Ackroyd S, Burns A, Timbs AT, et al. (February 2014). "SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage". Blood. 123 (7): 1021–31. doi:10.1182/blood-2013-04-490847. PMC   3924925 . PMID   24335234.
  30. ↑ Wang JL, Lu FZ, Shen XY, Wu Y, Zhao LT (December 2014). "SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation". Biochemical and Biophysical Research Communications. 455 (3–4): 229–33. doi:10.1016/j.bbrc.2014.10.153. PMID   25449277.
  31. ↑ de Silva S, Wang F, Hake TS, Porcu P, Wong HK, Wu L (February 2014). "Downregulation of SAMHD1 expression correlates with promoter DNA methylation in Sézary syndrome patients". The Journal of Investigative Dermatology. 134 (2): 562–5. doi:10.1038/jid.2013.311. PMC   3844041 . PMID   23884314.
  32. ↑ Kohnken R, Kodigepalli KM, Mishra A, Porcu P, Wu L (January 2017). "MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells derived from Sèzary syndrome patients". Leukemia Research. 52: 58–66. doi:10.1016/j.leukres.2016.11.010. PMC   5195900 . PMID   27889686.
  33. ↑ Pilakka-Kanthikeel S, Raymond A, Atluri VS, Sagar V, Saxena SK, Diaz P, Chevelon S, Concepcion M, Nair M (April 2015). "Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a". Journal of Neuroinflammation. 12: 66. doi:10.1186/s12974-015-0285-9. PMC   4410490 . PMID   25890101.
  34. ↑ Kretschmer S, Wolf C, König N, Staroske W, Guck J, Häusler M, Luksch H, Nguyen LA, Kim B, Alexopoulou D, Dahl A, Rapp A, Cardoso MC, Shevchenko A, Lee-Kirsch MA (March 2015). "SAMHD1 prevents autoimmunity by maintaining genome stability". Annals of the Rheumatic Diseases. 74 (3): e17. doi:10.1136/annrheumdis-2013-204845. PMC   4345975 . PMID   24445253.
  35. ↑ Kohnken R, Kodigepalli KM, Wu L (September 2015). "Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and therapeutic implications". Molecular Cancer. 14: 176. doi:10.1186/s12943-015-0446-6. PMC   4587406 . PMID   26416562.
  36. 1 2 Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF (December 2016). "Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs". Chemical Reviews. 116 (23): 14379–14455. doi:10.1021/acs.chemrev.6b00209. PMC   7717319 . PMID   27960273.
  37. ↑ Hollenbaugh JA, Shelton J, Tao S, Amiralaei S, Liu P, Lu X, Goetze RW, Zhou L, Nettles JH, Schinazi RF, Kim B (Jan 2017). "Substrates and Inhibitors of SAMHD1". PLOS ONE. 12 (1): e0169052. Bibcode:2017PLoSO..1269052H. doi: 10.1371/journal.pone.0169052 . PMC   5207538 . PMID   28046007.
  38. ↑ Schneider C, Oellerich T, Baldauf HM, Schwarz SM, Thomas D, Flick R, et al. (February 2017). "SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia" (PDF). Nature Medicine. 23 (2): 250–255. doi:10.1038/nm.4255. PMID   27991919. S2CID   205398095.
  39. ↑ Herold N, Rudd SG, Ljungblad L, Sanjiv K, Myrberg IH, Paulin CB, et al. (February 2017). "Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies". Nature Medicine. 23 (2): 256–263. doi:10.1038/nm.4265. PMID   28067901. S2CID   22800252.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.