Polyomaviridae: Diferenzas entre revisións
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Liña 53:
== Proteínas virais ==
=== Antíxenos tumorais (T) ===
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TO [[antíxeno tumoral grande]] xoga un papel clave na regulación do ciclo de vida viral ao unirse á orixe viral da replicación do ADN, onde promove a síntese de ADN. Ademais, como os poliomavirus dependen da maquinaria da célula hóspede para replicarse, a célula hóspede debe estar en fase S para que esta empece. Due to this, large T-antigen also modulates cellular signaling pathways to stimulate progression of the cell cycle by binding to a number of cellular control proteins.<ref>{{cite journal | vauthors = White MK, Gordon J, Reiss K, Del Valle L, Croul S, Giordano A, Darbinyan A, Khalili K | title = Human polyomaviruses and brain tumors | journal = Brain Research. Brain Research Reviews | volume = 50 | issue = 1 | pages = 69–85 | date = December 2005 | pmid = 15982744 | doi = 10.1016/j.brainresrev.2005.04.007 }}</ref> This is achieved by a two prong attack of inhibiting tumor suppressing genes p53 and members of the [[retinoblastoma protein|retinoblastoma]] (pRB) family,<ref>{{cite journal | vauthors = Kazem S, van der Meijden E, Wang RC, Rosenberg AS, Pope E, Benoit T, Fleckman P, Feltkamp MC | title = Polyomavirus-associated Trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21 | journal = PLOS One | volume = 9 | issue = 10 | pages = e108947 | year = 2014 | pmid = 25291363 | pmc = 4188587 | doi = 10.1371/journal.pone.0108947 | bibcode = 2014PLoSO...9j8947K }}</ref> and stimulating cell growth pathways by binding cellular DNA, ATPase-helicase, DNA polymerase α association, and binding of transcription preinitiation complex factors.<ref>{{cite journal | vauthors = Kelley WL, Georgopoulos C | title = The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens can functionally replace the J-domain of the Escherichia coli DnaJ molecular chaperone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 8 | pages = 3679–84 | date = April 1997 | pmid = 9108037 | pmc = 20500 | doi = 10.1073/pnas.94.8.3679 | bibcode = 1997PNAS...94.3679K }}</ref> This abnormal stimulation of the cell cycle is a powerful force for oncogenic transformation.▼
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The [[small tumor antigen]] protein is also able to activate several cellular pathways that stimulate cell proliferation. Polyomavirus small T antigens commonly target protein phosphatase 2A ([[PP2A]]),<ref>{{cite journal | vauthors = Pallas DC, Shahrik LK, Martin BL, Jaspers S, Miller TB, Brautigan DL, Roberts TM | title = Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A | journal = Cell | volume = 60 | issue = 1 | pages = 167–76 | date = January 1990 | pmid = 2153055 | doi = 10.1016/0092-8674(90)90726-u }}</ref> a key multisubunit regulator of multiple pathways including [[Akt]], the mitogen-activated protein kinase (MAPK) pathway, and the stress-activated protein kinase (SAPK) pathway.<ref>{{cite journal | vauthors = Sontag E, Fedorov S, Kamibayashi C, Robbins D, Cobb M, Mumby M | title = The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation | journal = Cell | volume = 75 | issue = 5 | pages = 887–97 | date = December 1993 | pmid = 8252625 | doi = 10.1016/0092-8674(93)90533-V | doi-access = free }}</ref><ref>{{cite journal | vauthors = Watanabe G, Howe A, Lee RJ, Albanese C, Shu IW, Karnezis AN, Zon L, Kyriakis J, Rundell K, Pestell RG | title = Induction of cyclin D1 by simian virus 40 small tumor antigen | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 23 | pages = 12861–6 | date = November 1996 | pmid = 8917510 | pmc = 24011 | doi = 10.1073/pnas.93.23.12861 | bibcode = 1996PNAS...9312861W }}</ref> [[Merkel cell polyomavirus]] small T antigen encodes a unique domain, called the LT-stabilization domain (LSD), that binds to and inhibits the [[FBXW7]] [[E3 ligase]] regulating both cellular and viral oncoproteins.<ref>{{cite journal | vauthors = Kwun HJ, Shuda M, Feng H, Camacho CJ, Moore PS, Chang Y | title = Merkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7 | journal = Cell Host & Microbe | volume = 14 | issue = 2 | pages = 125–35 | date = August 2013 | pmid = 23954152 | pmc = 3764649 | doi = 10.1016/j.chom.2013.06.008 }}</ref> Unlike for SV40, the MCV small T antigen directly transforms rodent cells in vitro.<ref>{{cite journal | vauthors = Shuda M, Kwun HJ, Feng H, Chang Y, Moore PS | title = Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator | journal = The Journal of Clinical Investigation | volume = 121 | issue = 9 | pages = 3623–34 | date = September 2011 | pmid = 21841310 | pmc = 3163959 | doi = 10.1172/JCI46323 }}</ref>
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