Cul1 promotes melanoma cell proliferation by promoting DEPTOR degradation and enhancing cap-dependent translation
| Autor: | Tianyu Liu, Yunhua Tu, Dongyun Rong, Yu Cao, Lan Chen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
RNA Caps Cancer Research Skin Neoplasms Ubiquitin-Protein Ligases Cell Cell Cycle Proteins mTORC1 Mechanistic Target of Rapamycin Complex 1 DEPTOR 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans RNA Small Interfering Melanoma Adaptor Proteins Signal Transducing biology Cell growth TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins Ubiquitination General Medicine Cell cycle Cullin Proteins Phosphoproteins Ubiquitin ligase Cell biology Neoplasm Proteins DNA-Binding Proteins 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Multiprotein Complexes Protein Biosynthesis Proteolysis biology.protein Cancer research CUL1 RNA Interference Protein Processing Post-Translational Cullin Cell Division Transcription Factors |
| Zdroj: | Oncology reports. 35(2) |
| ISSN: | 1791-2431 |
| Popis: | Cullin1 (Cul1) serves as a rigid scaffold in the SCF (Skp1/Cullin/Rbx1/F-box protein) E3 ubiquitin ligase complex and has been found to be overexpressed in melanoma and to enhance melanoma cell proliferation by promoting G1-S phase transition. However, the underlying mechanisms involved in the regulation of melanoma cell proliferation by Cul1 remain poorly understood. In the present study, we found that Cul1 promoted mTORC1 activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR. We further showed that suppression of the eIF4F complex assembly profoundly inhibited the promoting effect of Cul1 on melanoma cell proliferation, while enhancement of the eIF4F complex activity reversed the inhibitory effect of Cul1 depletion on melanoma cell proliferation, indicating that Cul1 contributes to melanoma cell proliferation by activating cap‑dependent translation. These data elucidate the role of Cul1 in cap-dependent translation and improves our understanding of the underlying mechanisms involved in the regulation of melanoma cell proliferation by Cul1. |
| Databáze: | OpenAIRE |
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