title: Cul1 promotes melanoma cell proliferation by promoting DEPTOR degradation and enhancing cap-dependent translation.
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.
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Rong
authors.affiliation: Department of Dermatology, The Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008545:Melanoma / Q000473:pathology*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012315:RNA Caps / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; C087000:EIF4EBP1 protein, human; C111931:ELF4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D012315:RNA Caps; D034741:RNA, Small Interfering; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C556139:DEPTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases