دورية أكاديمية
An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation
| العنوان: | An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation |
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| المؤلفون: | Simpson, Luke M., Fulcher, Luke J., Sathe, Gajanan, Brewer, Abigail, Zhao, Jin-Feng, Squair, Daniel R., Crooks, Jennifer, Wightman, Melanie, Wood, Nicola T., Gourlay, Robert, Varghese, Joby, Soares, Renata F., Sapkota, Gopal P. |
| المصدر: | Simpson , L M , Fulcher , L J , Sathe , G , Brewer , A , Zhao , J-F , Squair , D R , Crooks , J , Wightman , M , Wood , N T , Gourlay , R , Varghese , J , Soares , R F & Sapkota , G P 2023 , ' An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation ' , Cell Chemical Biology , vol. 30 , no. 2 , pp. 188-202 . https://doi.org/10.1016/j.chembiol.2023.01.003Test |
| سنة النشر: | 2023 |
| المجموعة: | Discovery - University of Dundee Online Publications |
| مصطلحات موضوعية: | Affinity-directed phosphatase, AdPhosphatase, Targeted dephosphorylation, PPP1CA, PPP2CA, Nanobody, ULK1, FAM83D, /dk/atira/pure/subjectarea/asjc/3000/3002, name=Drug Discovery, /dk/atira/pure/subjectarea/asjc/1300/1313, name=Molecular Medicine, /dk/atira/pure/subjectarea/asjc/1300/1312, name=Molecular Biology, /dk/atira/pure/subjectarea/asjc/1300/1303, name=Biochemistry, /dk/atira/pure/subjectarea/asjc/1300/1308, name=Clinical Biochemistry, /dk/atira/pure/subjectarea/asjc/3000/3004, name=Pharmacology |
| الوصف: | Reversible protein phosphorylation, catalyzed by protein kinases and phosphatases, is a fundamental process that controls protein function and intracellular signaling. Failure of phospho-control accounts for many human diseases. While a kinase phosphorylates multiple substrates, a substrate is often phosphorylated by multiple kinases. This renders phospho-control at the substrate level challenging, as it requires inhibition of multiple kinases, which would thus affect other kinase substrates. Here, we describe the development and application of the affinity-directed phosphatase (AdPhosphatase) system for targeted dephosphorylation of specific phospho-substrates. By deploying the Protein Phosphatase 1 or 2A catalytic subunits conjugated to an antigen-stabilized anti-GFP nanobody, we can promote the dephosphorylation of two independent phospho-proteins, FAM83D or ULK1, knocked in with GFP-tags using CRISPR-Cas9, with exquisite specificity. By redirecting protein phosphatases to neo-substrates through nanobody-mediated proximity, AdPhosphatase can alter the phospho-status and function of target proteins and thus, offers a new modality for potential drug discovery approaches. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://discovery.dundee.ac.uk/en/publications/b0ee5ed6-6d18-4e15-bd77-1c5b5ba96ccaTest |
| DOI: | 10.1016/j.chembiol.2023.01.003 |
| الإتاحة: | https://doi.org/10.1016/j.chembiol.2023.01.003Test https://discovery.dundee.ac.uk/en/publications/b0ee5ed6-6d18-4e15-bd77-1c5b5ba96ccaTest https://discovery.dundee.ac.uk/ws/files/96764889/1_s2.0_S2451945623000260_main.pdfTest http://www.scopus.com/inward/record.url?scp=85148030514&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.551A94C8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.chembiol.2023.01.003 |
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