. Author manuscript; available in PMC: 2015 Jan 26.

Published in final edited form as: Nat Rev Cancer. 2014 Apr;14(4):233–247. doi: 10.1038/nrc3700

Table 1.

Physiological, pathological and biochemical evidence for potential roles of highlighted F-box proteins in cancer

Evidence	F-box protein	Physiological evidence (mouse models for cancerous phenotypes)	Pathological evidence	Biochemical evidence (major substrates)
*Tumour suppressors*
Physiological, pathological and biochemical	FBXW7	Knockout^31,40 (tumorigenesis) Transgenic^34,36 (tumorigenesis upon expressing FBXW7 mutants)	Mutation^33,164,165	Cyclin E, MYC, JUN and MCL1
Physiological, pathological and biochemical	FBXO4	Knockout^62,61 (tumour or normal)	Mutation⁶⁴	Cyclin D1 and TRF1
*Emerging tumour suppressors*
Biochemical	FBXW8	Knockout^47,48 (embryonic lethal)^‡	CUL7 mutations in 3-M syndrome^‡ (REF. 166)	IRS1, TBC1D3 and cyclin D1
Pathological and biochemical	FBXL3	Knockout^‡ (REF. 134)	Mutation¹⁶⁷	CRY
Pathological and biochemical	FBXO1	Knockout⁵⁹ (embryonic lethal)^‡	Reduced expression⁶⁰	RRM2 and CP110
Pathological and biochemical	FBXO10	None	Associated with breast cancer risk^66–68	BCL-2
Physiological, pathological and biochemical	FBXO11	Jeff mouse (deaf and otitis media)⁴⁶	Associated with severe otitis media⁴⁶ and inactivated in diffuse large-B cell lymphoma¹¹	BCL-6 and CDT2
Physiological, pathological and biochemical	FBXO18	Fbxo18^f/f and Fbxo18^−/− (impaired mitotic progression following decatenation stress)¹⁶⁸	Deleted or mutated in melanoma cells⁶⁹	ATF1
Biochemical	FBXO31	Knockout⁶² (normal)^‡	None	Cyclin D1
*Oncogene*
Physiological, pathological and biochemical	SKP2	Knockout^79,81–83 (tumour resistant) Transgenic^76–78 (tumorigenesis)	Overexpression^169–171	p27, p21, RBL2 and FOXO1
*Emerging oncogenes*
Pathological and biochemical	FBXO5	Knockout⁹⁴ (embryonic lethal)^‡	Overexpression^96,97,101	Inhibitor of APC^CDH1 and APC^CDC20
Pathological and biochemical	FBXO9	None	Mutation¹⁰³	TELO2 and TTI1
*Context dependent*
Physiological, pathological and biochemical	β-TRCP1 and β-TRCP2	Knockout^106,172 (no tumour) Transgenic¹⁰⁷ (tumorigenesis in certain tissues)	Overexpression^110,173 (suggests oncogenic role) Mutation^112,113,174 (suggests tumour-suppressive role)	β-catenin, CDC25A, IκB and DEPTOR
Pathological and biochemical	FBXL10	Knockout^‡ (REF. 116)	Overexpression¹¹⁵	H2A
*Undetermined*
Pathological	FBXL2	Transgenic^‡ (REF. 175)	Overexpression¹⁷⁶	p85β and APP ^‡
Biochemical	FBXL5	Knockout^130,131 (embryonic lethal)^‡	None	p150^Glued and IRP2
Pathological	FBXL20	Knockout^‡ (REF. 177)	Overexpression¹³²	Not applicable
Biochemical	FBXL21	Knockout^‡ (REF. 134)	None	CRY
Biochemical	FBXO2	Knockout¹⁷⁸ (hearing loss)^‡	None	Pre-integrin β1, SHPS1 and NR1
Biochemical	FBXO7	Knockout^‡ (REF. 135)	None	CD43
Biochemical	FBXO15	Knockout¹⁴² (normal)^‡	None	MDR1
Biochemical and pathological	FBXO32	Knockout¹⁴⁵ Transgenic^‡ (REF. 145)	Reduced expression¹⁴⁷	MYOD1 and EIF3F
Biochemical	FBXO45	Knockout¹⁵¹ (embryonic lethal)^‡	None	p73 and UNC13A

APC, anaphase promoting complex; APP, amyloid-β A4 protein; ATF1, activating transcription factor 1; β-TRCP, β-transducin repeat-containing protein; BCL, B cell lymphoma; CP110, centrosomal protein of 110 kDa; CRY, cryptochrome; CUL7, cullin 7; DEPTOR, DEP domain-containing mTOR-interacting protein; EIF3F, eukaryotic translation initiation factor 3 subunit F; FBXL, F-box and leucine-rich repeat protein; FBXO, F-box only; FBXW, F-box/WD repeat-containing protein; FOXO1, forkhead box protein O1; H2A, histone H2A; IκB, inhibitor of nuclear factor-κB; IRP2, iron regulatory protein 2; IRS1, insulin receptor substrate 1; MCL1, myeloid cell leukaemia 1; MDR1, multidrug resistance protein 1; MYOD1, myoblast determination protein 1; NR1, N-methyl-d-aspartate receptor subunit NR1 (also known as NMDAR1); RBL2, retinoblastoma-like protein 2; RRM2, ribonucleotide reductase small subunit; SHPS1, SHP substrate 1; SKP2, S-phase kinase-associated protein 2; TBC1D3, TBC1 domain family member 3; TELO2, telomere maintenance 2; TRF1, telomeric repeat-binding factor 1; TTI1, TELO2-interacting protein 1; UNC13A, protein UNC-13 homologue A.

Indicates emerging tumour suppressors or oncoproteins.

^‡

Although data are shown in these cells, they are not supportive of a role in cancerous phenotypes.