Table 3 Major physiological roles of cullins revealed by deletion studies with model organisms

CUL1

Cell cycle and embryogenesis [66, 67], with KO phenotypes, including: embryonic lethality E5.5 to E6.5; accumulation of cyclin E; increased apoptosis in the ectoderm; large trophoblast giant cells in blastocytes

Cell cycle [1]; germline apoptosis [68]; sex determination [69]

Cell cycle [70, 71]; apoptosis [72]; eye development [73]

CUL2

No mouse model

G1-to-S transition [74]; mitosis [74, 75]; germline lineage [76]; meiosis [77–79]; polarity [77–79]; oogenesis [80]; MPK1 activation [80]; hypoxic response, aging [81, 82]

CUL3

Cell cycle and embryogenesis [83], with KO phenotypes including embryonic lethality <E7.5; accumulation of cyclin E; impaired S-phase entry; failure to endocycle in trophoblasts

Meiosis/mitosis transition [84]; mitosis [85]; meiosis [86]

Eye development [72]; sensory organ [87]; neurons [88]; hedgehog signaling [89, 90]; actin cytoskeleton and cell movement [91, 92]

CUL4

Deletion of Cul4a alone yields no major defects in development as mice lacking Cul4a exons 17 to 19 are viable and normal [93], and mice lacking Cul4a exons 4 to 8 are viable, showing mild decrease in mouse embryonic fibroblast proliferation [33]; a role in DNA repair as skin-specific CUL4A KO show increased resistance to UV-induced skin carcinogenesis [93]

DNA replication [22]

Cell cycle [94]; DNA damage response [95]

CUL5

No mouse model

Oogenesis [80]; MPK1 activation [80]

Cell fate specification [96]; synapse formation [96]; oogenesis [97]

CUL7

Embryonic development, as KO showed neonatal death [98]; required for growth in embryo and placenta [98]; formation of vascular structure [98]

PARC

Not essential for development, as KO is viable and normal [99]