The authors consider how knowledge of E3 ligase biology may be used for future therapeutic interventions in glioblastoma, including the use of blood-brain barrier permeable proteolysis targeting chimeras.
[Cell Death & Differentiation]
6445212 {6445212:I785429Q} apa 50 1 157774 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-bf4aaef7bd2a1ab409c4e40dfc3c66a8%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22I785429Q%22%2C%22library%22%3A%7B%22id%22%3A6445212%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Humphreys%20et%20al.%22%2C%22parsedDate%22%3A%222021-01-11%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EHumphreys%2C%20L.%20M.%2C%20Smith%2C%20P.%2C%20Chen%2C%20Z.%2C%20Fouad%2C%20S.%2C%20%26amp%3B%20D%26%23x2019%3BAngiolella%2C%20V.%20%282021%29.%20The%20role%20of%20E3%20ubiquitin%20ligases%20in%20the%20development%20and%20progression%20of%20glioblastoma.%20%3Ci%3ECell%20Death%20%26amp%3B%20Differentiation%3C%5C%2Fi%3E%2C%201%26%23x2013%3B16.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41418-020-00696-6%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41418-020-00696-6%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6445212%26amp%3Bitem_key%3DI785429Q%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22The%20role%20of%20E3%20ubiquitin%20ligases%20in%20the%20development%20and%20progression%20of%20glioblastoma%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Luke%20M.%22%2C%22lastName%22%3A%22Humphreys%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paul%22%2C%22lastName%22%3A%22Smith%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhuoyao%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shahd%22%2C%22lastName%22%3A%22Fouad%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vincenzo%22%2C%22lastName%22%3A%22D%5Cu2019Angiolella%22%7D%5D%2C%22abstractNote%22%3A%22Despite%20recent%20advances%20in%20our%20understanding%20of%20the%20disease%2C%20glioblastoma%20%28GB%29%20continues%20to%20have%20limited%20treatment%20options%20and%20carries%20a%20dismal%20prognosis%20for%20patients.%20Efforts%20to%20stratify%20this%20heterogeneous%20malignancy%20using%20molecular%20classifiers%20identified%20frequent%20alterations%20in%20targetable%20proteins%20belonging%20to%20several%20pathways%20including%20the%20receptor%20tyrosine%20kinase%20%28RTK%29%20and%20mitogen-activated%20protein%20kinase%20%28MAPK%29%20signalling%20pathways.%20However%2C%20these%20findings%20have%20failed%20to%20improve%20clinical%20outcomes%20for%20patients.%20In%20almost%20all%20cases%2C%20GB%20becomes%20refractory%20to%20standard-of-care%20therapy%2C%20and%20recent%20evidence%20suggests%20that%20disease%20recurrence%20may%20be%20associated%20with%20a%20subpopulation%20of%20cells%20known%20as%20glioma%20stem%20cells%5Cu00a0%28GSCs%29.%20Therefore%2C%20there%20remains%20a%20significant%20unmet%20need%20for%20novel%20therapeutic%20strategies.%20E3%20ubiquitin%20ligases%20are%20a%20family%20of%20%3E700%20proteins%20that%20conjugate%20ubiquitin%20to%20target%20proteins%2C%20resulting%20in%20an%20array%20of%20cellular%20responses%2C%20including%20DNA%20repair%2C%20pro-survival%20signalling%20and%20protein%20degradation.%20Ubiquitin%20modifications%20on%20target%20proteins%20are%20diverse%2C%20ranging%20from%20mono-ubiquitination%20through%20to%20the%20formation%20of%20polyubiquitin%20chains%20and%20mixed%20chains.%20The%20specificity%20in%20substrate%20tagging%20and%20chain%20elongation%20is%20dictated%20by%20E3%20ubiquitin%20ligases%2C%20which%20have%20essential%20regulatory%20roles%20in%20multiple%20aspects%20of%20brain%20cancer%20pathogenesis.%20In%20this%20review%2C%20we%20begin%20by%20briefly%20summarising%20the%20histological%20and%20molecular%20classification%20of%20GB.%20We%20comprehensively%20describe%20the%20roles%20of%20E3%20ubiquitin%20ligases%20in%20RTK%20and%20MAPK%2C%20as%20well%20as%20other%2C%20commonly%20altered%2C%20oncogenic%20and%20tumour%20suppressive%20signalling%20pathways%20in%20GB.%20We%20also%20describe%20the%20role%20of%20E3%20ligases%20in%20maintaining%20glioma%20stem%20cell%20populations%20and%20their%20function%20in%20promoting%20resistance%20to%20ionizing%20radiation%20%28IR%29%5Cu00a0and%20chemotherapy.%20Finally%2C%20we%20consider%20how%20our%20knowledge%20of%20E3%20ligase%20biology%20may%20be%20used%20for%20future%20therapeutic%20interventions%20in%20GB%2C%20including%20the%20use%20of%20blood%5Cu2013brain%20barrier%20permeable%20proteolysis%20targeting%20chimeras%5Cu00a0%28PROTACs%29.%22%2C%22date%22%3A%222021-01-11%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41418-020-00696-6%22%2C%22ISSN%22%3A%221476-5403%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41418-020-00696-6%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-01-11T17%3A16%3A32Z%22%7D%7D%5D%7D
Humphreys, L. M., Smith, P., Chen, Z., Fouad, S., & D’Angiolella, V. (2021). The role of E3 ubiquitin ligases in the development and progression of glioblastoma. Cell Death & Differentiation, 1–16. https://doi.org/10.1038/s41418-020-00696-6 Cite