Cul1 promotes melanoma cell proliferation by promoting DEPTOR degradation and enhancing cap-dependent translation.

Lan Chen, Tianyu Liu, Yunhua Tu, Dongyun Rong, Yu Cao

Index: Oncol. Rep. 35 , 1049-56, (2016)

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Abstract

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.