Increased Cul1 expression promotes melanoma cell proliferation through regulating p27 expression.
Cullin1 (Cul1) serves as a rigid scaffold in SCF (Skp1/Cullin/Rbx1/F-box protein) complex, the largest family of ubiquitin-protein E3 ligases, and aberrant expression of Cul1 is involved in dysfunction of SCF E3 ligases. Previously, we found that Cul1 expression is increased in early stages of melanoma. In the present study, we further investigated the role of Cul1 in melanoma development. Our results showed that knockdown of Cul1 inhibits melanoma cell growth while overexpression of Cul1 enhances cell proliferation through the control of cell cycle progression. We also found that Cul1 regulates melanoma cell growth and cell cycle progression through degradation of p27 by functional SCFSkp2 complex. This study elucidates the role of Cul1 in melanoma cell proliferation and improves our understanding of increased expression of Cul1 in early stages of melanoma.
Chen
Guangdi
G
Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, BC V6H 3Z6, Canada.
Li
Gang
G
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D044842:Cullin Proteins / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis* / Q000235:genetics
C100318:Cullin 1; D044842:Cullin Proteins; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen