FIGURE 3.

The upstream regulators of Fbxw7 and its major downstream targets that contributes to human tumorigenesis. Fbxw7 coordinates the ubiquitin-dependent proteolysis of several key oncoproteins, such as c-Myb,⁶ MED13,⁷ KLF2,⁸ KLF5,⁹ G-CSFR,¹⁰ eya1,¹¹ BCL-3,¹² NF1,¹³ NRF1,¹⁴ p100/NF-κB2,^15,16 GATA3,¹⁶ JunB,¹⁸ Mcl-1,^19,20 c-Myc,^21–27 CyclinE,^21–27 CDK2,¹⁶ Hes-1,¹⁶ CyclinD1,¹⁶ SREBP,²⁸ c-Jun,^23,29 HIF-1α,³⁰ Notch1,^23,31,32 DEK,²³ ENO1,³³ YAP,³⁴ mTOR,^35,36 Ki-67,^24,37 TOP2A,²⁰ CCDC6,³⁸ Aurora-A,^26,37,39 Notch4,³⁷ PCNA,³⁷ MYCN,⁴⁰ and their function linked to defects in cell proliferation, differentiation, genetic instability, and ultimately tumorigenesis. What is more, several proteins such as p53, RITA, EBP2, Numb4, SGK1, SREBP2, NF-κB1, Pin1, FAM83D, C/EBPδ, Hes-5, presenilin, miR-223, miR-25, miR-27a, miR-182, miR-503, miR-129-5p, and miR-92a are found to regulate the expression of Fbxw7. Aurora-A = Aurora kinase A, CCDC6 = coiled-coil-domain containing 6, ENO1 = Enolase 1, Fbxw7 = F-box/WD repeat-containing protein 7, G-CSFR = Granulocyte colony stimulating factor receptor, HIF-1α = Hypoxia inducible factor-1α, KLF2 = Kruppel-like factor 2, KLF5 = Kruppel-like factor 5, Mcl-1 = Myeloid cell leukemia-1, MED13 = Mediator 13, mTOR = mammalian target of rapamycin, NF1 = Neurofibromatosis type 1, NF-κB2 = p100/Nuclear factor-κB2, NRF1 = Nuclear factor E2-related factor 1, PCNA = proliferation cell nuclear antigen, SREBP = sterol regulatory element binding protein, YAP = Yes-associated proteins.