Cul7, a member of the DOC domain-containing cullin family, encodes an E3 ubiquitin ligase [1,2,4,5,7,9]. It is involved in multiple cellular processes such as cell transformation, apoptosis, and cell senescence [3]. It can assemble an SCF-ROC1-like E3 ubiquitin ligase complex, potentially defining an Fbx29-mediated and ubiquitin-dependent proteolysis pathway [9].

In glioma, Cul7 overexpression promotes tumorigenesis via NF-κB activation, while its knockdown inhibits tumor growth, invasion, and migration both in vitro and in vivo [1]. In cancer cells, Cul7 confers anti-apoptotic functions by promoting Caspase-8 ubiquitination at K215, and its knockdown sensitizes cells to TRAIL-induced apoptosis [2]. In B lymphocytes, Cul7 mediates the degradation of activation-induced cytidine deaminase, regulating Ig class switch recombination [4]. In non-small cell lung cancer, Cul7-mediated degradation of TET2 elicits EGFR-TKI resistance [5]. In addition, Cul7 may be involved in autism as transmitted mutations in it may create a sensitized background [6]. In chondro-tissue specific Cul7 knockout mice, knockout of Cul7 affects chondrocyte proliferation and endochondral osteogenesis, showing that Cul7 is essential for normal bone development [8].

In conclusion, Cul7 plays diverse and significant roles in multiple biological processes and disease conditions. The gene knockout and conditional knockout mouse models, like the chondro-tissue specific Cul7 knockout mice, have been instrumental in revealing its functions in diseases such as glioma, cancer, and in bone development. These models help in understanding the molecular mechanisms underlying these diseases, providing potential targets for treatment.