{"id":8819,"date":"2020-11-11T09:35:36","date_gmt":"2020-11-11T12:35:36","guid":{"rendered":"https:\/\/tdibrasil.org\/?p=8819"},"modified":"2026-06-15T19:41:26","modified_gmt":"2026-06-15T22:41:26","slug":"como-os-processos-celulares-reunem-e-descartam-proteinas-danificadas","status":"publish","type":"post","link":"https:\/\/tdibrasil.org\/index.php\/2020\/11\/11\/como-os-processos-celulares-reunem-e-descartam-proteinas-danificadas\/","title":{"rendered":"Como os Processos Celulares Re\u00fanem e Descartam Prote\u00ednas Danificadas"},"content":{"rendered":"<hr \/>\n<p>Por <strong>Eric Strieter<\/strong> (Phys.Org)<\/p>\n<p style=\"text-align: justify\">Em um novo artigo com resultados que o autor s\u00eanior Eric Strieter, da Universidade de Massachusetts Amherst, chama de \u201c<strong>incrivelmente<\/strong><strong>\u00a0<\/strong><strong>surpreendente<\/strong>\u201c, ele e seu grupo de laborat\u00f3rio de qu\u00edmica relataram que descobriram como uma enzima conhecida como UCH37 regula o\u00a0<strong>sistema<\/strong><strong>\u00a0<\/strong><strong>de<\/strong><strong>\u00a0<\/strong><strong>gerenciamento<\/strong>\u00a0de res\u00edduos de uma c\u00e9lula.<\/p>\n<p style=\"text-align: justify\">Strieter diz: \u201cLevamos oito anos para descobrir isso e estou muito orgulhoso desse trabalho. Tivemos que desenvolver muitos m\u00e9todos e ferramentas novos para\u00a0<strong>entender<\/strong>\u00a0o que essa enzima est\u00e1\u00a0<strong>fazendo<\/strong>.\u201d<\/p>\n<p style=\"text-align: justify\">Como ele explica, uma protease muito grande chamada proteassoma \u00e9\u00a0<strong>respons\u00e1vel<\/strong>\u00a0por\u00a0<strong>degradar<\/strong> a grande maioria das prote\u00ednas em uma c\u00e9lula; e ela pode ser feita de at\u00e9 40 prote\u00ednas. J\u00e1 se sabe h\u00e1 mais de 20 anos que a UCH37 \u00e9 uma das enzimas <strong>regulat\u00f3rias<\/strong> que se associam ao proteassoma, \u201cmas ningu\u00e9m entendia o que ela estava fazendo\u201c.<\/p>\n<p style=\"text-align: justify\">Acontece que o ponto crucial de todo o processo, acrescenta, \u00e9 o qu\u00e3o\u00a0<strong>complicadas<\/strong>\u00a0podem ser as\u00a0modifica\u00e7\u00f5es em uma pequena\u00a0<strong><a href=\"https:\/\/phys.org\/tags\/protein\/\" target=\"_blank\" rel=\"noopener noreferrer\">prote\u00edna<\/a><\/strong>\u00a0chamada ubiquitina.\u00a0\u201cAl\u00e9m de modificar outras prote\u00ednas, a ubiquitina se modifica, resultando em uma ampla gama de cadeias. Algumas dessas cadeias podem ter ramifica\u00e7\u00f5es extensas. Descobrimos que o UCH37\u00a0<strong>remove<\/strong>\u00a0pontos de ramifica\u00e7\u00e3o das cadeias,\u00a0<strong>permitindo<\/strong>\u00a0que a\u00a0<strong>degrada\u00e7\u00e3o<\/strong>\u00a0<strong>prossiga<\/strong>.\u201d<\/p>\n<p style=\"text-align: justify\">Escrevendo esta\u00a0semana\u00a0na\u00a0<strong>Molecular Cell<\/strong>, ele e o primeiro autor e Ph.D. Kirandeep Deol, que liderou e conduziu os experimentos, com os co-autores Sean Crowe, Jiale Du, Heather Bisbee e Robert Guenette, discutem como eles responderam \u00e0 pergunta. O trabalho foi apoiado pelo Instituto Nacional de Ci\u00eancias M\u00e9dicas Gerais do NIH.<\/p>\n<p style=\"text-align: justify\">Esse avan\u00e7o pode levar a um novo tratamento contra o c\u00e2ncer, diz Strieter, porque\u00a0<strong><a href=\"https:\/\/phys.org\/tags\/cancer+cells\/\" target=\"_blank\" rel=\"noopener noreferrer\">as c\u00e9lulas cancerosas<\/a> precisam<\/strong>\u00a0do proteassoma para crescer e proliferar.\u00a0\u201cMuitas c\u00e9lulas cancerosas s\u00e3o essencialmente dependentes\u00a0da\u00a0fun\u00e7\u00e3o do proteassoma\u201c, ressalta.\u00a0\u201cSuas c\u00e9lulas produzem prote\u00ednas em uma taxa t\u00e3o r\u00e1pida que\u00a0<strong>erros<\/strong><strong>\u00a0<\/strong><strong>s\u00e3o<\/strong><strong>\u00a0<\/strong><strong>cometidos<\/strong>\u00a0e, se eles n\u00e3o forem\u00a0<strong>eliminados<\/strong>, as c\u00e9lulas\u00a0<strong>n\u00e3o<\/strong><strong>\u00a0<\/strong><strong>podem<\/strong><strong>\u00a0<\/strong><strong>funcionar<\/strong>. Como o UCH37\u00a0<strong>ajuda<\/strong>\u00a0a\u00a0<strong>eliminar<\/strong>\u00a0as prote\u00ednas, pode ser um alvo terap\u00eautico \u00fatil para adicionar aos\u00a0<strong>inibidores<\/strong>\u00a0de proteassoma que j\u00e1 tiveram sucesso na cl\u00ednica.\u201d<\/p>\n<p style=\"text-align: justify\">Para come\u00e7ar seu processo de anos, Strieter diz, \u201ctivemos que encontrar uma maneira de gerar uma grande variedade de cadeias de ubiquitina que representassem a diversidade potencial em uma c\u00e9lula. Usar essa nova\u00a0<strong>biblioteca<\/strong>\u00a0de cadeias de ubiquitina nos permitiu interrogar a atividade da UCH37 em um\u00a0<strong>ambiente<\/strong>\u00a0<strong>controlado<\/strong>. Essa s\u00e9rie de experimentos nos deu a primeira pista de que essa enzima estava\u00a0<strong>fazendo<\/strong>\u00a0algo\u00a0<strong>\u00fanico<\/strong>.\u201d<\/p>\n<p style=\"text-align: justify\">Outro novo m\u00e9todo desenvolvido por eles usa\u00a0<strong><a href=\"https:\/\/phys.org\/tags\/mass+spectrometry\/\" target=\"_blank\" rel=\"noopener noreferrer\">espectrometria de massa<\/a><\/strong>\u00a0para caracterizar a arquitetura das cadeias de ubiquitina em\u00a0<strong>misturas complexas<\/strong>.\u00a0\u201cIsso nos permitiu ver que a atividade que descobrimos com nossa\u00a0<strong>biblioteca<\/strong>\u00a0de substratos tamb\u00e9m estava presente em uma mistura mais heterog\u00eanea\u201c, diz Strieter.\u00a0Finalmente, os qu\u00edmicos usaram a ferramenta de edi\u00e7\u00e3o do gene CRISPR para remover o UCH37 das c\u00e9lulas para medir o impacto do UCH37 na degrada\u00e7\u00e3o\u00a0<strong>mediada<\/strong>\u00a0por proteassoma in vitro e nas\u00a0<strong><a href=\"https:\/\/phys.org\/tags\/cells\/\" target=\"_blank\" rel=\"noopener noreferrer\">c\u00e9lulas<\/a><\/strong>.<\/p>\n<p style=\"text-align: justify\">Essa t\u00e9cnica trouxe mais uma surpresa.\u00a0\u201cEm vez de\u00a0<strong>agir<\/strong>\u00a0<strong>como<\/strong>\u00a0<strong>esperado<\/strong>\u00a0e se\u00a0<strong>opor<\/strong>\u00a0ao\u00a0<strong>processo<\/strong>\u00a0de\u00a0<strong>degrada\u00e7\u00e3o<\/strong>, descobriu-se que o UCH37 estava\u00a0<strong>removendo<\/strong>\u00a0<strong>pontos<\/strong>\u00a0de ramifica\u00e7\u00e3o das\u00a0cadeias de\u00a0<strong><a href=\"https:\/\/phys.org\/tags\/ubiquitin\/\" target=\"_blank\" rel=\"noopener noreferrer\">ubiquitina<\/a> para ajudar<\/strong>\u00a0a\u00a0<strong>degradar as prote\u00ednas<\/strong>\u201c, disse Strieter.\u00a0\u201cVoc\u00ea poderia pensar que removendo o\u00a0<strong>sinal<\/strong>\u00a0de degrada\u00e7\u00e3o essa degrada\u00e7\u00e3o seria\u00a0<strong>prejudicada<\/strong>\u201c, acrescenta ele, \u201cmas\u00a0<strong>n\u00e3o funcionou<\/strong>\u00a0dessa maneira.\u201d<\/p>\n<p style=\"text-align: justify\">Em experi\u00eancias futuras, Strieter e colegas esperam explorar ainda mais o processo de <strong><a href=\"https:\/\/phys.org\/tags\/degradation\/\" target=\"_blank\" rel=\"noopener noreferrer\">degrada\u00e7\u00e3o<\/a><\/strong>\u00a0e aprender mais detalhadamente\u00a0<strong>como<\/strong>\u00a0o UCH37\u00a0<strong>consegue regular<\/strong>\u00a0a\u00a0<strong>fun\u00e7\u00e3o<\/strong>\u00a0celular.<\/p>\n<hr \/>\n<p><strong>Mais informa\u00e7\u00f5es:<\/strong>\u00a0Kirandeep K. Deol et al, Proteasome-Bound UCH37 \/ UCHL5 Debranches Ubiquitin Chains to Promover Degradation,\u00a0Molecular Cell\u00a0(2020).\u00a0<a href=\"https:\/\/dx.doi.org\/10.1016\/j.molcel.2020.10.017\" target=\"_blank\" rel=\"noopener noreferrer\">DOI: 10.1016 \/ j.molcel.2020.10.017<\/a><\/p>\n<p><strong>Informa\u00e7\u00e3o do di\u00e1rio:<\/strong>\u00a0<a href=\"https:\/\/phys.org\/journals\/molecular-cell\/\">Molecular Cell<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<div class=\"mh-excerpt\"><p>Uma protease muito grande (proteassoma) \u00e9\u00a0respons\u00e1vel\u00a0por\u00a0degradar a maioria das prote\u00ednas em uma c\u00e9lula. A UCH37 \u00e9 uma das enzimas que se associam ao proteassoma, \u201cmas ningu\u00e9m entendia o que ela estava fazendo\u201c.<\/p>\n<\/div>","protected":false},"author":15,"featured_media":8820,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25,40],"tags":[1050,343,781],"class_list":["post-8819","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-geral","category-traducao","tag-arquitetura-de-proteinas","tag-enzima","tag-proteinas"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Como os Processos Celulares Re\u00fanem e Descartam Prote\u00ednas Danificadas &#187; Portal TDI Brasil +<\/title>\n<meta name=\"description\" content=\"Uma protease muito grande (proteassoma) \u00e9\u00a0respons\u00e1vel\u00a0por\u00a0degradar a maioria das prote\u00ednas em uma c\u00e9lula. 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