E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration

Table 1

E3 ubiquitin ligases and bone metabolism.

Broad group of ligase	Name	Function	References
HECT	SMURF1	Inhibits osteoblast differentiation and mineralization	[15–23, 25, 26, 28–33]
HECT	SMURF2	Inhibits osteoblast differentiation; enhances osteoclast differentiation; inhibits angiogenesis; stimulates endochondral ossification	[34–39]
HECT	Nedd4-1	Enhances osteogenic differentiation	[62–64]
HECT	Nedd4-2	Inhibits osteoblast differentiation and mineralization	[65]
HECT	WWP1	Inhibits osteoblast differentiation and mineralization	[35, 66–68]
HECT	WWP2	Enhances osteogenic differentiation	[69–71]
HECT	Itch	Inhibits or enhances osteogenic differentiation; inhibits osteoclastogenesis	[84–87]
RING	APC/C^CDH1	Inhibits osteoblast differentiation and mineralization	[42]
RING	APC/C^CDC20	Enhances osteogenic differentiation	[41]
RING	TRAF4	Enhances osteogenic differentiation	[43]
RING	TRAF6	Enhances osteoclast differentiation	[44–46]
RING	TRIM21	Inhibits osteogenic differentiation	[51]
RING	TRIM33	Protects osteoblasts against oxidative stress-induced apoptosis in osteoporosis	[52, 53]
RING	TRIM38	Enhances osteogenic differentiation; inhibits osteoclastogenesis	[54]
RING	RNF40	Enhances osteogenic differentiation	[56, 57]
RING	RNF146	Enhances osteogenic differentiation; inhibits osteoclastogenesis	[58–60]
RING	RNF185	Inhibits osteoblast differentiation and mineralization	[61]
RING	Mdm2	Enhances osteogenic differentiation	[76, 77]
RING	Cbl-b and c-Cbl	Inhibits osteoblast differentiation and mineralization; enhances osteogenic differentiation	[6, 91–95]
RING	LNX2	Enhances osteoclast differentiation	[99]
RING	Arkadia	Enhances osteogenic differentiation	[105]
B-box	TRIM16	Enhances osteogenic differentiation	[49, 50]
F-box	SCF^Skp2	Inhibits osteoblast differentiation and mineralization	[80]
F-box	FBL12	Inhibits osteoblast differentiation and mineralization	[96, 97]
U-box	CHIP	Inhibits osteoblast differentiation and mineralization; inhibits osteoclastogenesis	[88, 89]
RBR	Parkin	Enhances osteogenic differentiation	[102, 103]