Table 1.

Targets/substrates of F-box proteins and their biological functions

F-box protein	Localization	Role	Substrates	Biological functions
FBXL gene family
SKP2	Nucleus,Cytoplasm	Oncogene	RELN	EMT 16
			CARM1	AMPK pathway 18
			AKT (K63)	AKT Pathway 167
			PDCD4	Apoptosis 34
			P21	Cell cycle 23
			P27	Cell cycle 22
			P130	Cell cycle 27
			c-Myc	Cell cycle 26
			Cyclin E	Cell cycle 25
			FOXO1	FOXO signaling pathway 33
			YAP1 (K63)	Transcription of target genes 35
FBXL2	Cytoplasm, Membrane	Potential tumor suppressor	Cyclin D	Cell cycle checkpoints42, 43
			AURKB	Cell cycle checkpoints44
			p85β	PI3K pathway 7
			IP3R3	PI3K pathway 11
			FOXM1	Cell proliferation 45
FBXL3	Nucleus, Cytoplasmic	Potential tumor suppressor	CRY1,CRY2	Circadian clock system 49
			c-Myc	Cell cycle progression, apoptosis and cellular transformation 50
			TLK2	Cell cycle 51
FBXL4	Cytoplasm, Mitochondrion, Nucleus	Potential tumor suppressor	KDM4A	Replication time 52
			RDL	Timing of sleep 53
FBXL5	Cytoplasm, Perinuclear region	Potential tumor suppressor	IRP1,IRP2	Iron metabolism 56 168
			p150	Genome stability59
			SNAIL1	EMT 60
			CITED2	HIF pathway 61
			hSSB1	DNA repair 62
FBXL7	Cytoskeleton	Potential oncogene	AURKA	Cell cycle 63
			Survivin	Apoptosis 65
FBXL12	Cytoplasm, Nucleus	Unclear	ALDH3	T cell development 70
			Ku80	Non homologues end joining double strand break repair mechanism 169
			CaMKI	Cell cycle 68
			p21	Cell cycle progression at G1 69
FBXL13	Cytoskeleton, Cytoplasm	Potential oncogene	CEP192	Centrosome duplication 72
FBXL14	Cytoplasm	Potential tumor suppressor	CDCP1	Tyrosine phosphorylation-dependent regulation of cellular events 77
			SNAIL1	EMT 75
			c-Myc	Cell cycle progression, apoptosis and cellular transformation 76
			HES1	Neuron development 78
			TWIST1	EMT 74
FBXL15	Cytoplasm	Unclear	SMURF1	BMP signaling pathway 12
FBXL17	Nucleus, Cytoplasm	Potential oncogene	SUFU	Hedgehog signal pathway79
			BACH1	NRF2 oxidative stress pathway 14
FBXL18	Cytoplasm, Nucleus	Potential oncogene	XPB	Transcription 81
			AKT(K63)	AKT pathway 15
FBXL19	Cytoplasm	Potential tumor suppressor	RAC3	TGFβ1-induced E-cadherin down-regulation 83
			RhoA	Cell proliferation and cytoskeleton rearrangement 84
FBXL20	Cytoplasm	Potential oncogene	E-cadherin	Wnt signaling pathway 87
			Vps34	Autophagy 86
FBXL21	Cytoplasm, Nucleus	Unclear	CRY1,CRY2	Circadian clock system 88
FBXW gene family
β-TrCP	Nucleus, Cytoplasm	Generally oncogene & tumor suppressor in a few cases	β-catenin	Cell viability 90
			IκBα	NF-κB pathway 93
			CDC25A	Cell cycle 94
			REST	Spindle check points 96
			MCL1	Anti-apoptotic (a member of the Bcl-2 family) 97
			p53	p53 pathway 101
			c-Myc	Apoptosis 99
			Lipin1	Fatty acid biosynthesis 100
			MTSS1	Tumour suppression 104
			NRF2	NRF2 pathway 98
			FBXW2	β-TrCP-FBXW2-SKP2 axis 102
			ZNF281	Colorectal cancer progression 103
			DEPTOR, REDD1	Autophagy 105
FBXW7	FBXWα: Nucleoplasm, FBXWβ: Cytoplasm, FBXWγ:Nucleolus	Tumor suppressor	Cyclin E	Cell cycle 106
			mTOR	mTOR signaling pathway 110
			NOTCH1	NOTCH1 signaling 114
			c-Jun and DEK	Closed circularity of DNA, cell cycle progression 112
			MCL1	Apoptosis 111
			c-Myc	Cell proliferation 109
FBXW2	Cytoplasm	Potential tumor suppressor	SKP2	β-TrCP-FBXW2-SKP2 axis 102
			β-catenin	116
FBXW5	Cytoplasm, Nucleus	Unclear	SASS6	Centrosome duplication 118
			EPS8	Cell proliferation and motility 119
			TSC2	Tuberous sclerosis 117
FBXW8	Golgi apparatus, Cytoplasm	Unclear	MAP4K1	MAPK pathway 120
FBXO gene family
FBXO1	Nucleus, Cytoplasm, Cytoskeleton	Potential tumor suppressor	RRM2	DNA replication and DNA repair synthesis 122
			CP110	Centrosome duplication; Genomic integrity 121
			NUSAP1	Chromosome assembly 123
			CDC6	Early steps of DNA replication 124
FBXO3	Nucleus, Cytoplasm	Unclear	AIRE	T cell development 128
			HIPK2,p300	Transcription 126
			SMRUF1	BMP signaling pathway 129
FBXO4	Cytoplasm	Tumor suppressor	TRF1	Cell cycle 131
			MCL1	Apoptosis 137
			FXR1	RNA binding protein and Fragile X syndrome 134
			ICAM1	Intercellular adhesion 136
			PPARγ	Adipocyte differentiation 138
			Cyclin D1	Cell cycle 130
FBXO6	Cytoplasm	Unclear	CHK1	Cisplatin sensitivity 140
			MAD2,BUBR1	Spindle checkpoint 142
			Ero1L	Apoptosis 141
FBXO7	Cytoplasm, Mitochondrion, Nucleus	Potential oncogene	cIAP1	Inhibition of apoptosis 146
FBXO10	Cytoplasm	Potential tumor suppressor	BCL1	Apoptosis 170
FBXO11	Chromosome, Nucleus	Potential tumor suppressor	HIF-1α	HIF-1αsignaling pathway 143
			BCL6	B-cells differentiation 147
			SNAIL	EMT 148
FBXO21	Cytoplasm	Unclear	EID1	Cell cycle 164
FBXO22	Cytoplasm, Nucleus, Z disc	Unclear	ACTN2, FLNC	Contractile function 165
FBXO31	Cytoplasm, Cytoskeleton	Potential tumor suppressor	SNAIL1	EMT 153
			Cyclin D1	Cell cycle 152
			MDM2	p53-mediated growth arrest 154
			MKK6	MAPK pathway 155
FBXO32	Cytoplasm, Nucleus	Unclear	KLF4	Apoptosis 156
			IκBα	NF-κB pathway 157
			CTBP1	EMT 158
FBXO38	Cytoplasm, Nucleus	Potential tumor suppressor	PD-1	Immunity of T cells 166
FBXO45	Postsynaptic cell membrane , Cell junction, Synapse	Unclear	N-Cadherin	Neuronal differentiation 163
			PAR4	Apoptosis 161
			p73	Apoptosis 162

Note: other unlisted F-box proteins have no known substrates at present. The potential roles of F-box proteins, mostly context dependent, are just based on current limited studies.