| http://purl.uniprot.org/citations/32345600 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32345600 | http://www.w3.org/2000/01/rdf-schema#comment | "F-box proteins, such as F-box/WD repeat-containing protein 7 (FBW7), are essential components of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases. They bind to S-phase kinase-associated protein 1 (SKP1) through the F-box motif and deliver their protein substrate to the E3 ligase complex for ubiquitination and subsequent degradation. F-box and leucine-rich repeat protein 16 (FBXL16) is a poorly studied F-box protein. Because it does not interact with the scaffold protein cullin 1 (CUL1), we hypothesized that FBXL16 might not form a functional SCF-E3 ligase complex. In the present study, we found that FBXL16 up-regulates the levels of proteins targeted by SCF-E3 ligases, such as C-MYC, β-catenin, and steroid receptor coactivator 3 (SRC-3). Focusing on C-MYC, a well-known oncoprotein overexpressed in most human cancers, we show that FBXL16 stabilizes C-MYC by antagonizing FBW7-mediated C-MYC ubiquitination and degradation. Further, we found that, although FBXL16 does not interact with CUL1, it interacts with SKP1 via its N-terminal F-box domain and with its substrate C-MYC via its C-terminal leucine-rich repeats (LRRs) domain. We found that both the F-box domain and the LRR domain are important for FBXL16-mediated C-MYC stabilization. In line with its role in up-regulating the levels of the C-MYC and SRC-3 oncoproteins, FBXL16 promoted cancer cell growth and migration and colony formation in soft agar. Our findings reveal that FBXL16 is an F-box protein that antagonizes the activity of another F-box protein, FBW7, and thereby increases C-MYC stability, resulting in increased cancer cell growth and invasiveness."xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra120.012658"xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/author | "Morel M."xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/author | "Long W."xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/author | "Shah K.N."xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/pages | "7970-7980"xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/title | "The F-box protein FBXL16 up-regulates the stability of C-MYC oncoprotein by antagonizing the activity of the F-box protein FBW7."xsd:string |
| http://purl.uniprot.org/citations/32345600 | http://purl.uniprot.org/core/volume | "295"xsd:string |
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