El grup de Biologia de la Cromatina de l’IDIBELL, liderat per \u00c0lex Vaquero, estudia el paper d\u2019una fam\u00edlia de prote\u00efnes anomenades sirtu\u00efnes en la resposta a l\u2019estr\u00e8s metab\u00f2lic i genot\u00f2xic i la seva contribuci\u00f3 al desenvolupament de malalties com el c\u00e0ncer i el control de l\u2019envelliment.<\/p>\n
En aquest estudi realitzat amb la col\u00b7laboraci\u00f3 del grup de la investigadora Lourdes Serrano de l\u2019Institut de Gen\u00e8tica Humana de la Universitat Rutgers de New Jersey (EUA) i que es publica avui a la revista Genes & Development, els investigadors descriuen els mecanismes epigen\u00e8tics mitjan\u00e7ant els quals una d\u2019aquestes prote\u00efnes, la sirtu\u00efna 2 (SirT2) regula la progressi\u00f3 del cicle cel\u00b7lular i l\u2019estabilitat gen\u00f2mica.<\/p>\n
<\/p>\n
Aplicacions cl\u00edniques de SirT2<\/strong><\/p>\n En els \u00faltims anys les sirtu\u00efnes, especialment SirT1 i SirT2, s\u2019han relacionat amb les malalties neurodegeneratives ja qu\u00e8 un dels m\u00faltiples factors que est\u00e0 darrere d\u2019aquests desordres \u00e9s l\u2019estr\u00e8s oxidatiu i el principal mecanisme de resposta de les nostres c\u00e8l\u00b7lules a aquestes condicions est\u00e0 regulat per aquestes prote\u00efnes.<\/p>\n Segons ha explicat \u00c0lex Vaquero, \u201csembla que SirT1 tindria un paper m\u00e9s protector contra aquests tipus d\u2019estr\u00e8s mentre que SirT2 tindria en molts casos un efecte contrari. La ind\u00fastria farmac\u00e8utica busca f\u00e0rmacs inhibidors de SirT2 per utilitzar-los contra aquestes malalties\u201d. L\u2019investigador adverteix que \u201cper aquest motiu \u00e9s important con\u00e8ixer la funci\u00f3 de supressor de tumors de SirT2, ja qu\u00e8 s\u2019hauria de tenir en compte a l\u2019hora d\u2019oferir-la com a tractament\u201d.<\/p>\n <\/p>\n Control de les marques epigen\u00e8tiques<\/strong><\/p>\n Les modificacions epigen\u00e8tiques s\u00f3n marques qu\u00edmiques situades en el genoma que provoquen canvis en l\u2019expressi\u00f3 dels gens. Una d\u2019aquestes marques, l\u2019acetilaci\u00f3 de l\u2019amino\u00e0cid lisina 16 de la prote\u00efna histona H4 (H4K16Ac), sembla ser particularment important per regular l\u2019organitzaci\u00f3 i la integritat del genoma. Aix\u00ed doncs, l\u2019alteraci\u00f3 d\u2019aquesta marca provoca inestabilitat del genoma i ha estat relacionada directament amb el c\u00e0ncer.<\/p>\n Fa uns anys, les investigacions de Vaquero ja van demostrar que SirT2 regula l\u2019eliminaci\u00f3 d\u2019aquesta marca epigen\u00e8tica just abans de comen\u00e7ar el proc\u00e9s de divisi\u00f3 cel\u00b7lular (mitosi), probablement per permetre una compactaci\u00f3 adequada dels cromosomes durant la mitosi.<\/p>\n En l\u2019estudi que es publica ara a Genes & Development, els investigadors de l\u2019IDIBELL han aprofundit en aquesta relaci\u00f3 funcional entre SirT2, aquesta marca epigen\u00e8tica i la mitosi, per intentar entendre les conseq\u00fc\u00e8ncies que l\u2019activitat de SirT2 i la p\u00e8rdua de la marca epigen\u00e8ticaH4K16Ac tenen durant la mitosi i el cicle cel\u00b7lular en general.<\/p>\n El grup de Vaquero ha descobert que la desacetilaci\u00f3 (l\u2019eliminaci\u00f3 de la marca qu\u00edmica) de la lisina 16 a la histona 4 per part de SirT2 promou l\u2019activitat de l\u2019enzim PR-Set7 que t\u00e9 com a missi\u00f3 dipositar una altra marca epigen\u00e8tica, la metilaci\u00f3, en una posici\u00f3 molt propera a K16, la lisina 20 de la mateixa histona H4 (H4K20me1). SirT2 no nom\u00e9s regula l\u2019activitat de PR-Set7 eliminant H4K16Ac, tamb\u00e9 desacetila PR-Set7 permetent l\u2019expansi\u00f3 d\u2019aquesta marca al llarg del genoma i en quins punts s\u2019ha d\u2019acumular. \u201cAquestes marques\u201d ha explicat Vaquero \u201cs\u00f3n clau en el proc\u00e9s de replicaci\u00f3 i reparaci\u00f3 de l\u2019ADN, en la progressi\u00f3 de la mitosis), i en la compactaci\u00f3 de la cromatina\u201d.<\/p>\n \u201cSirT2 actua com a agent controlador: fins que no hi ha les condicions adequades no continua el cicle cel\u00b7lular\u201d ha explicat Vaquero. \u201cHem comprovat en ratolins que en abs\u00e8ncia de SirT2, es pot fer la mitosi i la divisi\u00f3 cel\u00b7lular per\u00f2 que s\u2019acumula dany gen\u00e8tic i augmenten els nivells d\u2019inestabilitat gen\u00f2mica. De manera que aquests animals s\u00f3n m\u00e9s propensos a desenvolupar tumors\u201d.<\/p>\n \u201cEn aquest treball\u201d ha dit l\u2019investigador \u201chem trobat el mecanisme que confirma i explica les propietats antitumorals de SirT2 i que relaciona encara m\u00e9s la funci\u00f3 de les sirtu\u00efnes amb el control de la mem\u00f2ria epigen\u00e8tica de la c\u00e8l\u00b7lula\u201d.<\/p>\n <\/p>\n <\/p>\n Refer\u00e8ncia de l\u2019article<\/strong><\/p>\n Serrano L., Mart\u00ednez-Redondo P.*, Marazuela-Duques A.*, V\u00e1zquez N. B., Dooley S.J., Voigt P., Beck D.B.*, Kane-Goldsmith N., Tong Q., Rabanal R.M., Fondevila D., Mu\u00f1oz P.*, Kr\u00fcger M., Tischfield J.A. and Vaquero A.*. The Tumor supressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation.<\/strong> Genes&Development. Published in Advance <\/em>March 6, 2013<\/em>, doi:<\/em>10.1101\/gad.211342.112<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" El grup de Biologia de la Cromatina de l’IDIBELL, liderat per \u00c0lex Vaquero, estudia el paper d\u2019una fam\u00edlia de prote\u00efnes anomenades sirtu\u00efnes en la resposta a l\u2019estr\u00e8s metab\u00f2lic i genot\u00f2xic i la seva contribuci\u00f3 al desenvolupament de malalties com el c\u00e0ncer i el control de l\u2019envelliment. En aquest estudi realitzat amb la col\u00b7laboraci\u00f3 del grup […]<\/p>\n","protected":false},"author":6,"featured_media":20554,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[376],"tags":[],"class_list":["post-8577","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-epigenetica-del-cancer"],"publishpress_future_action":{"enabled":false,"date":"2024-11-30 00:08:16","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8577","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=8577"}],"version-history":[{"count":2,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8577\/revisions"}],"predecessor-version":[{"id":20555,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/8577\/revisions\/20555"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/20554"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=8577"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=8577"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=8577"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}