2019
DOI: 10.3390/cancers11020246
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FBXW7 in Cancer: What Has Been Unraveled Thus Far?

Abstract: : The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene FBXW7 is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system (UPS) thus regulating cellular growth. FBXW7 is considered as a potent tumor suppressor as most of its target substrates can function as potential growth promoters, including c-Myc, Notch, cyclin E, c-JUN, and KLF5. Its regulators include p53, C/EBP-δ, Numb, micr… Show more

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Cited by 132 publications
(108 citation statements)
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References 201 publications
(273 reference statements)
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“…FBXW7 is a potential tumor suppressor, and mutations in the gene are thought to impair cyclin E degradation resulting in uncontrolled cell division and growth, thus resulting in cancer progression [29]. A previous study suggested that a missense mutation was correlated with poor OS in CRC patients [30].…”
Section: Discussionmentioning
confidence: 99%
“…FBXW7 is a potential tumor suppressor, and mutations in the gene are thought to impair cyclin E degradation resulting in uncontrolled cell division and growth, thus resulting in cancer progression [29]. A previous study suggested that a missense mutation was correlated with poor OS in CRC patients [30].…”
Section: Discussionmentioning
confidence: 99%
“…NEDD8 conjugation facilitates the CRL structural remodeling that will juxtapose the substrate toward the catalytically active ubiquitylation site of CRL (40)(41)(42). The substrate receptor protein, docked in the CRL complex by binding to the adaptor protein, recruits substrates for Ub conjugation once CRL is fully functional (43) (Figure 1). So far, seven different types of human cullin proteins (CUL1, 2, 3, 4A, 4B, 5, 7) have been identified, and new members of the receptor and adaptor proteins are emerging (44).…”
Section: Neddylation Inhibition Nedd8 Conjugation Pathwaymentioning
confidence: 99%
“…F-box WD repeat domain-containing-7 (FBXW7) encodes for the F-box protein with seven tandem WD40 and is located at chromosome 4q31.3. It is one of the vital substrate-recognition subunits of ubiquitin ligase called the Skp1-Cdc53/Cullin-F-box-protein complex (SCF/β-TCP) [90,91]. The Catalogue of Somatic Mutations in Cancer (COSMIC) database identified that FBXW7 has the highest frequency of mutation in both F-box and WD repeat domain-containing family members and SCF ubiquitin ligase complexes, with a mutation percentage of 2.54 % [92].…”
Section: Fbxw7 Mutationsmentioning
confidence: 99%