دورية أكاديمية
Biochemical characterization of the interaction between KRAS and Argonaute 2
| العنوان: | Biochemical characterization of the interaction between KRAS and Argonaute 2 |
|---|---|
| المؤلفون: | Jessica J. Waninger, Tyler S. Beyett, Varun V. Gadkari, Ronald F. Siebenaler, Carson Kenum, Sunita Shankar, Brandon T. Ruotolo, Arul M. Chinnaiyan, John J.G. Tesmer |
| المصدر: | Biochemistry and Biophysics Reports, Vol 29, Iss , Pp 101191- (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Biochemistry |
| مصطلحات موضوعية: | Biology (General), QH301-705.5, Biochemistry, QD415-436 |
| الوصف: | Oncogenic mutations in KRAS result in a constitutively active, GTP-bound form that in turn activates many proliferative pathways. However, because of its compact and simple architecture, directly targeting KRAS with small molecule drugs has been challenging. Another approach is to identify targetable proteins that interact with KRAS. Argonaute 2 (AGO2) was recently identified as a protein that facilitates RAS-driven oncogenesis. Whereas previous studies described the in vivo effect of AGO2 on cancer progression in cells harboring mutated KRAS, here we sought to examine their direct interaction using purified proteins. We show that full length AGO2 co-immunoprecipitates with KRAS using purified components, however, a complex between FL AGO2 and KRAS could not be isolated. We also generated a smaller N-terminal fragment of AGO2 (NtAGO2) which is believed to represent the primary binding site of KRAS. A complex with NtAGO2 could be detected via ion-mobility mass spectrometry and size exclusion chromatography. However, the data suggest that the interaction of KRAS with purified AGO2 (NtAGO2 or FL AGO2) is weak and likely requires additional cellular components or proteo-forms of AGO2 that are not readily available in our purified assay systems. Future studies are needed to determine what conformation or modifications of AGO2 are necessary to enrich KRAS association and regulate its activities. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-5808 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2405580821002855; https://doaj.org/toc/2405-5808 |
| DOI: | 10.1016/j.bbrep.2021.101191 |
| URL الوصول: | https://doaj.org/article/5afdc55c4e9a499fb8675d06a6b666e1 |
| رقم الأكسشن: | edsdoj.5afdc55c4e9a499fb8675d06a6b666e1 |
| قاعدة البيانات: | Directory of Open Access Journals |
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