التفاصيل البيبلوغرافية
| العنوان: |
Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress |
| المؤلفون: |
Pitts, Stephanie, Liu, Hester, Ibrahim, Adel, Garg, Amit, Felgueira, Catarina Mendes, Begum, Asma, Fan, Wenjun, Teh, Selina, Low, Jin Yih, Ford, Brittany, Schneider, David A., Hay, Ronald, Laiho, Marikki |
| المساهمون: |
Drug Research Program, TRIMM - Translational Immunology Research Program, Doctoral Programme in Drug Research, Faculty of Pharmacy |
| بيانات النشر: |
American Society for Biochemistry and Molecular Biology |
| سنة النشر: |
2023 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
cancer, proteasome, small molecule, transcription, ubiquitin, Biomedicine, Cancers |
| الوصف: |
RNA Polymerase I (Pol I) synthesizes rRNA, which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing Pol I inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degradation of the largest subunit of Pol I, RPA194. To identify the E3 ligase(s) involved, we conducted a cell-based RNAi screen for ubiquitin pathway genes. We establish Skp–Cullin–F-box protein complex F-box protein FBXL14 as an E3 ligase for RPA194. We show that FBXL14 binds to RPA194 and mediates RPA194 ubiquitination and degradation in cancer cells treated with BMH-21. Mutation analysis in yeast identified lysines 1150, 1153, and 1156 on Rpa190 relevant for the protein degradation. These results reveal the regulated turnover of Pol I, showing that the stability of the catalytic subunit is controlled by the F-box protein FBXL14 in response to transcription stress. ; Peer reviewed |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
This work was supported by grants from the National Cancer Institute , National Institutes of Health (NIH; grant nos.: F31CA247077 to S. P. and P30CA006973 to M. L.) and National Institute of General Medical Sciences , NIH (grant no.: R01GM121404 to M. L. and D. A. S.). The content in this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.; Pitts , S , Liu , H , Ibrahim , A , Garg , A , Felgueira , C M , Begum , A , Fan , W , Teh , S , Low , J Y , Ford , B , Schneider , D A , Hay , R & Laiho , M 2022 , ' Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress ' , Journal of Biological Chemistry , vol. 298 , no. 12 , 102690 . https://doi.org/10.1016/j.jbc.2022.102690; http://hdl.handle.net/10138/354858; 7ca57775-5b1d-45dc-ad09-6f8981c89981; 85143584740 |
| الاتاحة: |
http://hdl.handle.net/10138/354858 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: |
edsbas.D641EAEB |
| قاعدة البيانات: |
BASE |