{"id":8362,"date":"2026-05-06T08:15:16","date_gmt":"2026-05-06T06:15:16","guid":{"rendered":"https:\/\/www.iqac.csic.es\/una-nova-estrategia-experimental-permet-eliminar-proteines-implicades-en-processos-patologics\/"},"modified":"2026-06-16T10:47:43","modified_gmt":"2026-06-16T08:47:43","slug":"una-nova-estrategia-experimental-permet-eliminar-proteines-implicades-en-processos-patologics","status":"publish","type":"post","link":"https:\/\/www.iqac.csic.es\/ca\/una-nova-estrategia-experimental-permet-eliminar-proteines-implicades-en-processos-patologics\/","title":{"rendered":"Una nova estrat\u00e8gia experimental permet eliminar prote\u00efnes implicades en processos patol\u00f2gics"},"content":{"rendered":"<p>Un estudi en fase precl\u00ednica dut a terme per <a href=\"https:\/\/www.iqac.csic.es\/\" target=\"_blank\" rel=\"noopener\">l\u2019Institut de Qu\u00edmica Avan\u00e7ada de Catalunya (IQAC)<\/a> i <a href=\"https:\/\/ibmb.csic.es\/en\/\" target=\"_blank\" rel=\"noopener\">l\u2019Institut de Biologia Molecular de Barcelona (IBMB)<\/a>, tots dos del <a href=\"https:\/\/www.csic.es\/es\" target=\"_blank\" rel=\"noopener\">CSIC<\/a>, ha desenvolupat una estrat\u00e8gia que permet for\u00e7ar l\u2019eliminaci\u00f3 de prote\u00efnes que ajuden els tumors a sobreviure a la quimioter\u00e0pia. La troballa obre una nova via per fer front a la resist\u00e8ncia als tractaments contra el c\u00e0ncer, un dels principals reptes de l\u2019oncologia. La recerca, publicada a la revista <em><a href=\"https:\/\/www.nature.com\/articles\/s41467-026-71132-5\" target=\"_blank\" rel=\"noopener\">Nature Communications<\/a><\/em>, suposa una prova de concepte d\u2019un nou mecanisme de degradaci\u00f3 indu\u00efda de prote\u00efnes nocives, que amplia les possibilitats de desenvolupar ter\u00e0pies m\u00e9s eficaces en el futur.<\/p>\n<blockquote><p>\u201cEls nostres resultats presenten una metodologia experimental optimitzada, alternativa a la via convencional de degradaci\u00f3 indu\u00efda. Aquest enfocament permetria dissenyar tractaments m\u00e9s precisos contra malalties com el c\u00e0ncer, aix\u00ed com superar o fins i tot revertir la quimioresist\u00e8ncia en determinats casos\u201d, explica <strong>Bernat Crosas<\/strong>, investigador del CSIC a l\u2019IBMB, que ha liderat la recerca juntament amb <strong>Gemma Fabri\u00e0s<\/strong>, investigadora de l\u2019IQAC-CSIC i del CIBEREHD, i <strong>Jordi Bujons<\/strong>, de l\u2019IQAC-CSIC. En el treball tamb\u00e9 hi ha participat personal investigador de la Universitat de Barcelona.<\/p><\/blockquote>\n<h4><strong>Sistema de reciclatge de prote\u00efnes<\/strong><\/h4>\n<p>Les nostres c\u00e8l\u00b7lules disposen d\u2019una sofisticada maquin\u00e0ria encarregada d\u2019eliminar prote\u00efnes defectuoses o innecess\u00e0ries: el sistema ubiquitina-proteasoma, que constitueix una via de reciclatge del material proteic. En aquest proc\u00e9s, les prote\u00efnes que han de ser destru\u00efdes s\u00f3n \u201cetiquetades\u201d amb una mol\u00e8cula, la ubiquitina, de manera que s\u00f3n reconegudes i degradades pel proteasoma, un org\u00e0nul present en totes les c\u00e8l\u00b7lules.<\/p>\n<p>En els darrers anys s\u2019han desenvolupat noves eines, encara experimentals, per eliminar prote\u00efnes nocives de l\u2019organisme basant-se en la intervenci\u00f3 del proteasoma. Una d\u2019aquestes s\u00f3n els anomenats Protacs (de l\u2019angl\u00e8s <em>Proteolytic Targeting Chimeras<\/em>), mol\u00e8cules dissenyades per desencadenar el proc\u00e9s d\u2019etiquetatge de les prote\u00efnes diana amb ubiquitina i induir-ne la destrucci\u00f3. Tanmateix, aquest enfocament presenta limitacions, ja que dep\u00e8n de mecanismes cel\u00b7lulars molt espec\u00edfics que no sempre funcionen correctament.<\/p>\n<blockquote><p>\u201cEl proc\u00e9s convencional funciona com un sistema de recollida de residus: primer s\u2019etiqueten els \u2018residus\u2019 amb unitats d\u2019ubiquitina i despr\u00e9s es transporten fins a la planta de reciclatge, el proteasoma\u201d, explica <strong>Mireia Casasampere<\/strong>, investigadora de l\u2019IQAC-CSIC i primera autora del treball. \u201cNo obstant aix\u00f2, aquest sistema pot no ser del tot eficient, ja que dep\u00e8n de diversos passos intermedis des de l\u2019etiquetatge fins a l\u2019eliminaci\u00f3 de la prote\u00efna\u201d, afegeix.<\/p><\/blockquote>\n<h4><strong>Drecera per digerir la \u201cbrossa\u201d cel\u00b7lular<\/strong><\/h4>\n<p>Aquesta recerca explora una estrat\u00e8gia alternativa basada a esquivar la fase d\u2019etiquetatge i enviar les prote\u00efnes directament al proteasoma. \u201cEn aquest cas, portem les prote\u00efnes directament al sistema de reciclatge cel\u00b7lular\u201d, explica <strong>Tania Roda<\/strong>, tamb\u00e9 investigadora de l\u2019IQAC-CSIC.<\/p>\n<p>L\u2019equip ha dissenyat i sintetitzat noves mol\u00e8cules tipus Protac capaces de dirigir cap al proteasoma dues prote\u00efnes rellevants en c\u00e0ncer, sense requerir l\u2019etapa interm\u00e8dia d\u2019ubiquitinaci\u00f3: IMPDH2, una enzima clau en la replicaci\u00f3 cel\u00b7lular i, per tant, relacionada amb el creixement tumoral, i CERT1, una prote\u00efna transportadora lip\u00eddica implicada en processos de mort de les c\u00e8l\u00b7lules tumorals. Les mol\u00e8cules Protacs dissenyades s\u00f3n modulars: una part reconeix la prote\u00efna que es vol eliminar (IMPDH2 o CERT1), mentre que l\u2019altra es connecta amb una part\u00edcula del proteasoma (USP14) que en regula l\u2019activitat.<\/p>\n<p>Tal com explica <strong>Gemma Fabri\u00e0s<\/strong>, \u201cs\u00f3n mol\u00e8cules d\u2019alta afinitat que s\u2019uneixen a la prote\u00efna diana i la vehiculen fins al lloc prec\u00eds on ser\u00e0 degradada i destru\u00efda\u201d. Es tracta d\u2019un mecanisme d\u2019acci\u00f3 m\u00e9s simple i eficient. El resultat \u00e9s la inactivaci\u00f3 de la c\u00e8l\u00b7lula tumoral, que ja no pot replicar-se, o b\u00e9 la seva mort per apoptosi.<\/p>\n<h4><strong>Degradaci\u00f3 dirigida<\/strong><\/h4>\n<p>Les proves realitzades amb c\u00e8l\u00b7lules canceroses han demostrat l\u2019efectivitat i el potencial d\u2019aquesta nova estrat\u00e8gia de degradaci\u00f3 dirigida, evitant algunes de les limitacions de les tecnologies existents, que depenen de mecanismes cel\u00b7lulars espec\u00edfics que no sempre funcionen correctament en determinats contextos patol\u00f2gics.<\/p>\n<p>A m\u00e9s, els resultats suggereixen que, en eliminar CERT1, les c\u00e8l\u00b7lules tumorals recuperen la sensibilitat a alguns tractaments de quimioter\u00e0pia. \u201cSi es bloqueja CERT1 en alguns carcinomes, la quimioter\u00e0pia pot tornar a funcionar. Tot i que els nostres resultats s\u00f3n molt preliminars, obren una possible via perqu\u00e8 els tumors tornin a respondre als tractaments, reduint la resist\u00e8ncia, un problema molt com\u00fa en c\u00e0ncer. De fet, en alguns tipus de c\u00e0ncer, entre el 60% i el 90% dels pacients poden desenvolupar resist\u00e8ncia a la quimioter\u00e0pia, una situaci\u00f3 que es pot agreujar en casos de met\u00e0stasi\u201d, conclou <strong>Bernat Crosas<\/strong>.<\/p>\n<p>Actualment, l\u2019equip est\u00e0 centrat a optimitzar aquestes mol\u00e8cules per millorar-ne l\u2019efic\u00e0cia i l\u2019especificitat, aix\u00ed com a explorar la seva aplicaci\u00f3 en models m\u00e9s avan\u00e7ats amb vista a una possible aplicaci\u00f3 cl\u00ednica.<\/p>\n<p>Aquest enfocament, tot i ser preliminar, \u00e9s molt prometedor i amplia les eines disponibles per a la degradaci\u00f3 dirigida de prote\u00efnes, i podria contribuir al desenvolupament de futures ter\u00e0pies m\u00e9s precises contra malalties complexes com el c\u00e0ncer, o altres patologies en qu\u00e8 s\u2019hagi identificat una prote\u00efna diana.<\/p>\n<p>Aquesta recerca ha estat finan\u00e7ada pel Ministeri de Ci\u00e8ncia, Innovaci\u00f3 i Universitats, i pels fons Next Generation de la Uni\u00f3 Europea, a trav\u00e9s de la Plataforma PTI Salut Global del CSIC i la Generalitat de Catalunya.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"font-size: 75%;\">Casasampere, M., Carneros, H., Roda, T.\u00a0<em>et al.<\/em>\u00a0<strong>Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome<\/strong>.\u00a0<em>Nat Commun<\/em>\u00a0(2026). <a href=\"https:\/\/doi.org\/10.1038\/s41467-026-71132-5\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1038\/s41467-026-71132-5<\/a><\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p style=\"text-align: right;\"><strong>Ana Sotres \/ IQAC-CSIC Comunicaci\u00f3<\/strong><\/p>\n<p style=\"text-align: right;\"><strong>CSIC Comunicaci\u00f3 Catalu\u00f1a<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Un estudi en fase precl\u00ednica dut a terme per l\u2019Institut de Qu\u00edmica Avan\u00e7ada de Catalunya (IQAC) i l\u2019Institut de Biologia Molecular de Barcelona (IBMB), tots dos del CSIC, ha desenvolupat una estrat\u00e8gia que permet for\u00e7ar l\u2019eliminaci\u00f3 de prote\u00efnes que ajuden els tumors a sobreviure a la quimioter\u00e0pia. La troballa obre una nova via per fer<a class=\"more-link\" href=\"https:\/\/www.iqac.csic.es\/ca\/una-nova-estrategia-experimental-permet-eliminar-proteines-implicades-en-processos-patologics\/\">Continue reading <span class=\"screen-reader-text\">\u00abUna nova estrat\u00e8gia experimental permet eliminar prote\u00efnes implicades en processos patol\u00f2gics\u00bb<\/span><\/a><\/p>\n","protected":false},"author":3,"featured_media":4594,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[73],"tags":[],"class_list":["post-8362","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","entry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Una nova estrat\u00e8gia experimental permet eliminar prote\u00efnes implicades en processos patol\u00f2gics | IQAC - Institut de Qu\u00edmica Avan\u00e7ada de Catalunya - CSIC<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.iqac.csic.es\/ca\/una-nova-estrategia-experimental-permet-eliminar-proteines-implicades-en-processos-patologics\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Una nova estrat\u00e8gia experimental permet eliminar prote\u00efnes implicades en processos patol\u00f2gics | IQAC - Institut de Qu\u00edmica Avan\u00e7ada de Catalunya - CSIC\" \/>\n<meta property=\"og:description\" content=\"Un estudi en fase precl\u00ednica dut a terme per l\u2019Institut de Qu\u00edmica Avan\u00e7ada de Catalunya (IQAC) i l\u2019Institut de Biologia Molecular de Barcelona (IBMB), tots dos del CSIC, ha desenvolupat una estrat\u00e8gia que permet for\u00e7ar l\u2019eliminaci\u00f3 de prote\u00efnes que ajuden els tumors a sobreviure a la quimioter\u00e0pia. 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