Abstract
FBW7 (F-box and WD repeat domain-containing 7) or Fbxw7 is a tumor suppressor, which promotes the ubiquitination and subsequent degradation of numerous oncoproteins including Mcl-1, Cyclin E, Notch, c- Jun, and c-Myc. In turn, FBW7 is regulated by multiple upstream factors including p53, C/EBP-δ, EBP2, Pin1, Hes-5 and Numb4 as well as by microRNAs such as miR-223, miR-27a, miR-25, and miR-129-5p. Given that the Fbw7 tumor suppressor is frequently inactivated or deleted in various human cancers, targeting FBW7 regulators is a promising anti-cancer therapeutic strategy.
Highlights
FBW7 (F-box and WD repeat domain-containing 7), known as Fbxw7, has been found to be involved in numerous cellular processes including cell proliferation, apoptosis, cell cycle and differentiation [1,2,3]
KLF2 has been shown to exert cell growth-inhibitory, proapoptotic and anti-angiogenic functions. Consistent with this notion, KLF2 expression is diminished in a variety of human malignancies including prostate, breast, and ovarian cancers, suggesting that KLF2 may be a tumor suppressor gene [63]
Study has suggested that Numb binds to and inhibits the E3 ubiquitin ligase Mdm2, which is responsible for p53 degradation, subsequently leading to up-regulation of p53 [146, 147]
Summary
FBW7 (F-box and WD repeat domain-containing 7), known as Fbxw, has been found to be involved in numerous cellular processes including cell proliferation, apoptosis, cell cycle and differentiation [1,2,3]. Recent studies have identified various downstream ubiquitin targets for FBW7, relatively little is known about the upstream signaling pathways that control FBW7 stability and cellular functions. MED13 and MED13L are identified as bona fide FBW7 substrates These important findings further suggested that FBW7 represents a novel mechanism for regulation of the Mediator activity to possibly influence the whole transcriptome [62]. KLF2 has been shown to exert cell growth-inhibitory, proapoptotic and anti-angiogenic functions Consistent with this notion, KLF2 expression is diminished in a variety of human malignancies including prostate, breast, and ovarian cancers, suggesting that KLF2 may be a tumor suppressor gene [63]. These reports suggest that G-CSFR could be a substrate of FBW7 and aberrant upregulation of G-CSFR due to impairments in FBW7-mediated destruction could contribute to the development of AML
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
