Pathogenic roles of the Cullin E3 ligase scaffolding protein CUL4B

CUL4B belongs to the Cullin family, the members of which are scaffolding proteins of Cullin-RING E3 ligases (CRLs), the largest ubiquitin ligase complex in eukaryotes. CUL4B is a scaffolding protein of Cullin 4B-RING ubiquitin ligase complex (CRL4B), which catalyzes the polyubiquitination or monoubiquitination of substrate proteins and plays important roles in various physiological and pathophysiological processes. The fact that mutations in CUL4B are causally associated with human mental retardation syndrome opened a new direction for the study on the function of CUL4B. Using cell models, it was found that the CRL4B complex plays important roles in regulating cell proliferation and DNA damage repair. At the same time, it was found that CUL4B is highly expressed in various solid tumor tissues, and regulates tumor progression by epigenetically regulating the transcription of multiple tumor suppressor genes. Research using mouse models found that CUL4B played important roles in embryonic development, nervous system development, germ cell development, myeloid cell differentiation, adipocyte differentiation, and pancreatic delta cell function. This review will summarize our current knowledge of CUL4B in the pathogenesis in human diseases and mouse models.