pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase
| العنوان: | pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase |
|---|---|
| المؤلفون: | Katherine A. Donovan, Charles M. Ponthier, Ragna Sack, Jan Seebacher, Michael B. Stadler, Eric S. Fischer, Jian An |
| المصدر: | Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017) |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Science, General Physics and Astronomy, Protein degradation, Proteomics, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Ubiquitin, Stable isotope labeling by amino acids in cell culture, medicine, Lenalidomide, Zinc finger, Multidisciplinary, biology, 010405 organic chemistry, Chemistry, General Chemistry, Pomalidomide, 0104 chemical sciences, 3. Good health, Ubiquitin ligase, Cell biology, 030104 developmental biology, biology.protein, medicine.drug |
| الوصف: | Thalidomide and its derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of haematologic malignancies. It was shown that IMiDs impart gain-of-function properties to the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) ubiquitin ligase that enable binding, ubiquitination and degradation of key therapeutic targets such as IKZF1, IKZF3 and CSNK1A1. While these substrates have been implicated as efficacy targets in multiple myeloma (MM) and 5q deletion associated myelodysplastic syndrome (del(5q)-MDS), other targets likely exist. Using a pulse-chase SILAC mass spectrometry-based proteomics approach, we demonstrate that lenalidomide induces the ubiquitination and degradation of ZFP91. We establish ZFP91 as a bona fide IMiD-dependent CRL4CRBN substrate and further show that ZFP91 harbours a zinc finger (ZnF) motif, related to the IKZF1/3 ZnF, critical for IMiD-dependent CRBN binding. These findings demonstrate that single time point pulse-chase SILAC mass spectrometry-based proteomics (pSILAC MS) is a sensitive approach for target identification of small molecules inducing selective protein degradation. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b823fce410ca4d850e7ed97e8c58b6b https://doaj.org/article/29e7aa9bcbbf457cab317eff9b4c1bbd |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1b823fce410ca4d850e7ed97e8c58b6b |
| قاعدة البيانات: | OpenAIRE |
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