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Keywords = FBXW7/FBW7/Cdc4/SEL-10

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11 pages, 1749 KB  
Review
The Highs and Lows of FBXW7: New Insights into Substrate Affinity in Disease and Development
by Claire C. de la Cova
Cells 2023, 12(17), 2141; https://doi.org/10.3390/cells12172141 - 24 Aug 2023
Cited by 3 | Viewed by 3048
Abstract
FBXW7 is a critical regulator of cell cycle, cell signaling, and development. A highly conserved F-box protein and component of the SKP1–Cullin–F-box (SCF) complex, FBXW7 functions as a recognition subunit within a Cullin–RING E3 ubiquitin ligase responsible for ubiquitinating substrate proteins and targeting [...] Read more.
FBXW7 is a critical regulator of cell cycle, cell signaling, and development. A highly conserved F-box protein and component of the SKP1–Cullin–F-box (SCF) complex, FBXW7 functions as a recognition subunit within a Cullin–RING E3 ubiquitin ligase responsible for ubiquitinating substrate proteins and targeting them for proteasome-mediated degradation. In human cells, FBXW7 promotes degradation of a large number of substrate proteins, including many that impact disease, such as NOTCH1, Cyclin E, MYC, and BRAF. A central focus for investigation has been to understand the molecular mechanisms that allow the exquisite substrate specificity exhibited by FBXW7. Recent work has produced a clearer understanding of how FBXW7 physically interacts with both high-affinity and low-affinity substrates. We review new findings that provide insights into the consequences of “hotspot” missense mutations of FBXW7 that are found in human cancers. Finally, we discuss how the FBXW7–substrate interaction, and the kinases responsible for substrate phosphorylation, contribute to patterned protein degradation in C. elegans development. Full article
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27 pages, 1641 KB  
Review
The Role of FBXW7 in Gynecologic Malignancies
by Riccardo Di Fiore, Sherif Suleiman, Rosa Drago-Ferrante, Yashwanth Subbannayya, Sarah Suleiman, Mariela Vasileva-Slaveva, Angel Yordanov, Francesca Pentimalli, Antonio Giordano and Jean Calleja-Agius
Cells 2023, 12(10), 1415; https://doi.org/10.3390/cells12101415 - 17 May 2023
Cited by 9 | Viewed by 5174
Abstract
The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial [...] Read more.
The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs. Full article
(This article belongs to the Special Issue Biomarkers for Diagnosis and Treatment of Gynecologic Neoplasms)
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