دورية أكاديمية
The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling
| العنوان: | The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling |
|---|---|
| المؤلفون: | Chakraborty, Atanu, Diefenbacher, Markus E, Mylona, Anastasia, Kassel, Olivier, Behrens, Axel |
| المصدر: | Chakraborty , A , Diefenbacher , M E , Mylona , A , Kassel , O & Behrens , A 2015 , ' The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling ' , Nature Communications , vol. 6 , 6782 . https://doi.org/10.1038/ncomms7782Test |
| سنة النشر: | 2015 |
| المجموعة: | King's College, London: Research Portal |
| مصطلحات موضوعية: | Animals, Apoptosis, Carrier Proteins/metabolism, Cell Line, Tumor, Cell Proliferation, HEK293 Cells, HeLa Cells, Humans, Lung Neoplasms/metabolism, MAP Kinase Signaling System, Mice, Transgenic, Neoplasm Transplantation, Phosphorylation, Proto-Oncogene Proteins c-jun/metabolism, Proto-Oncogene Proteins c-myc/metabolism, Ribosomal Protein S6 Kinases, 90-kDa/metabolism, Signal Transduction, Trans-Activators/metabolism, Transcription Factor AP-1/metabolism, Ubiquitin-Protein Ligases/metabolism, Ubiquitination, raf Kinases/metabolism, ras Proteins/metabolism |
| الوصف: | The c-Jun/AP-1 transcription factor controls key cellular behaviours, including proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While the JNK pathway has been well characterized, the mechanism of activation by Ras was elusive. Here we identify the uncharacterized ubiquitin ligase Trim7 as a critical component of AP-1 activation via Ras. We found that MSK1 directly phosphorylates Trim7 in response to direct activation by the Ras-Raf-MEK-ERK pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity. Trim7 mediates Lys63-linked ubiquitination of the AP-1 co-activator RACO-1, leading to RACO-1 protein stabilization. Consequently, Trim7 depletion reduces RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer model, and knockdown of Trim7 in established xenografts reduces tumour growth. Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1 completes the long sought-after mechanism linking growth factor signalling and AP-1 activation. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1038/ncomms7782 |
| الإتاحة: | https://doi.org/10.1038/ncomms7782Test https://kclpure.kcl.ac.uk/portal/en/publications/889ee695-fd2d-43d5-9e23-8fd433c8fd29Test https://kclpure.kcl.ac.uk/ws/files/131218447/The_E3_ubiquitin_ligase_Trim7_Accepted26Feb2015_ePublished8Apr2015_GOLD_VoR_CC_BY_.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.EED716D6 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ncomms7782 |
|---|