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SAMHD1
ββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββ
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SAMHD1 (englisch SAM domain and HD domain-containing protein 1) ist eine Phosphohydrolase und ein Resistenzfaktor gegen Lentiviren.
Contents
β’ Eigenschaften
β’ Literatur
β’ Einzelnachweise
ββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββ
Eigenschaften
SAMHD1 hemmt die Replikation von HIV in dendritischen Zellen,cite-ref-1[1] Makrophagencite-ref-2[2] und Monozytencite-ref-3[3] von Primaten. Die Hemmung erfolgt durch die Hydrolyse von dNTPs zu Nukleosiden und Triphosphat, die dann nicht mehr fΓΌr die reverse Transkriptase bei der Replikation zur VerfΓΌgung stehen.cite-ref-4[4] SAMHD1 besitzt zudem eine an der HIV-Resistenz beteiligte 3'β5'-Exonuklease-AktivitΓ€tcite-ref-5[5] und eine RNase-AktivitΓ€t.cite-ref-6[6] HIV besitzt das Protein Vpx zur Immunevasion durch Hemmung von SAMHD1.cite-ref-7[7]
In teilenden Zellen wird SAMHD1 durch Phosphorylierung an T592 inaktiviert, wΓ€hrend es in ruhenden Zellen aktiv ist.cite-ref-8[8]
SAMHD1 ist an der Entstehung des Aicardi-Goutières-Syndroms beteiligt.cite-ref-9[9]
Literatur
β’ A. Sze, D. Olagnier, R. Lin, J. van Grevenynghe, J. Hiscott: SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection. In: Journal of molecular biology. Band 425, Nummer 24, Dezember 2013, ISSN 1089-8638, S. 4981β4994, doi:10.1016/j.jmb.2013.10.022, PMID 24161438.
Einzelnachweise
cite-note-11. β N. Laguette, B. Sobhian, N. Casartelli, M. Ringeard, C. Chable-Bessia, E. SΓ©gΓ©ral, A. Yatim, S. Emiliani, O. Schwartz, M. Benkirane: SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. In: Nature. Band 474, Nummer 7353, Juni 2011, ISSN 1476-4687, S. 654β657, doi:10.1038/nature10117, PMID 21613998, PMC 3595993 (freier Volltext).
cite-note-22. β K. Hrecka, C. Hao, M. Gierszewska, S. K. Swanson, M. Kesik-Brodacka, S. Srivastava, L. Florens, M. P. Washburn, J. Skowronski: Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. In: Nature. Band 474, Nummer 7353, Juni 2011, ISSN 1476-4687, S. 658β661, doi:10.1038/nature10195, PMID 21720370, PMC 3179858 (freier Volltext).
cite-note-33. β A. Berger, A. F. Sommer, J. Zwarg, M. Hamdorf, K. Welzel, N. Esly, S. Panitz, A. Reuter, I. Ramos, A. Jatiani, L. C. Mulder, A. Fernandez-Sesma, F. Rutsch, V. Simon, R. KΓΆnig, E. Flory: SAMHD1-deficient CD14+ cells from individuals with Aicardi-GoutiΓ¨res syndrome are highly susceptible to HIV-1 infection. In: PLoS pathogens. Band 7, Nummer 12, Dezember 2011, ISSN 1553-7374, S. e1002425, doi:10.1371/journal.ppat.1002425, PMID 22174685, PMC 3234228 (freier Volltext).
cite-note-44. β H. Lahouassa, W. Daddacha, H. Hofmann, D. Ayinde, E. C. Logue, L. Dragin, N. Bloch, C. Maudet, M. Bertrand, T. Gramberg, G. Pancino, S. Priet, B. Canard, N. Laguette, M. Benkirane, C. Transy, N. R. Landau, B. Kim, F. Margottin-Goguet: SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. In: Nature Immunology. Band 13, Nummer 3, MΓ€rz 2012, ISSN 1529-2916, S. 223β228, doi:10.1038/ni.2236, PMID 22327569, PMC 3771401 (freier Volltext).
cite-note-55. β N. Beloglazova, R. Flick, A. Tchigvintsev, G. Brown, A. Popovic, B. Nocek, A. F. Yakunin: Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction. In: The Journal of biological chemistry. Band 288, Nummer 12, MΓ€rz 2013, ISSN 1083-351X, S. 8101β8110, doi:10.1074/jbc.M112.431148, PMID 23364794, PMC 3605629 (freier Volltext).
cite-note-66. β J. Ryoo, J. Choi, C. Oh, S. Kim, M. Seo, S. Y. Kim, D. Seo, J. Kim, T. E. White, A. Brandariz-NuΓ±ez, F. Diaz-Griffero, C. H. Yun, J. A. Hollenbaugh, B. Kim, D. Baek, K. Ahn: The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. In: Nature medicine. Band 20, Nummer 8, August 2014, ISSN 1546-170X, S. 936β941, doi:10.1038/nm.3626, PMID 25038827, PMC 4318684 (freier Volltext).
cite-note-88. β T. E. White, A. Brandariz-NuΓ±ez, J. C. Valle-Casuso, S. Amie, L. A. Nguyen, B. Kim, M. Tuzova, F. Diaz-Griffero: The retroviral restriction ability of SAMHD1, but not its deoxynucleotide triphosphohydrolase activity, is regulated by phosphorylation. In: Cell host & microbe. Band 13, Nummer 4, April 2013, ISSN 1934-6069, S. 441β451, doi:10.1016/j.chom.2013.03.005, PMID 23601106, PMC 3864637 (freier Volltext).