The evolutionarily conserved cullin family proteins can assemble as many as 400 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. CUL4, one of three founding cullins conserved from yeast to humans, uses a large beta …

2022年12月19日 · 研究表明，IMiDs主要通过结合CRL4 E3泛素连接酶 (CRL4CRBN) 复合物的底物受体蛋白Cereblon (CRBN) 发挥其抗骨髓瘤活性。 通过结合CRBN，IMiDs改变了其底物的特性，导致骨髓瘤细胞存活所必需的蛋白质的泛素化和蛋白酶体降解。

Here, the work provides an overview to address the role of CRL4 E3 ubiquitin ligase in cancer development and progression, and discuss the possible mechanisms of CRL4 ligase involving in many cellular processes associated with tumor.

2015年12月15日 · Here, the work provides an overview to address the role of CRL4 E3 ubiquitin ligase in cancer development and progression, and discuss the possible mechanisms of CRL4 ligase involving in many cellular processes associated with tumor. Finally, we discuss its potential value in cancer therapy.

In this article, we will discuss the genetic function, molecular assembly and substrates of CUL4– RING ligases (CRL4s). We will compare CUL4’s pleiotropic functions across several species, and review the current model for CUL4 assembly with its linker protein DDB1 (for damaged DNA binding) and its family of WD40 containing substrate receptors.

2024年11月22日 · Our findings reveal that circRFWD2_369aa plays a crucial role in regulating the expression and ubiquitination of p27 in MM cells by forming complexes with DDB1 and CUL4A as an E3 ligase.

2009年10月8日 · Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor

2009年11月1日 · In this article we discuss the genetic function, molecular assembly and substrates of CUL4–RING ligases (CRL4s). We compare the pleiotropic functions of CUL4 across several species and review the current model for CUL4 assembly with its linker protein DDB1 (for damaged DNA binding) and its family of WD40-containing substrate receptors.

2022年9月16日 · It is now known that IMiDs exert their anti-myeloma activity mainly by binding cereblon (CRBN), the substrate receptor protein of the CRL4 E3 ubiquitin ligase (CRL4 CRBN) complex. By binding CRBN, IMiDs alter its substrate specificity, leading to ubiquitination and proteasomal degradation of proteins essential for MM cell survival.

Based on evidence from knockout and transgenic mouse models, human clinical data, and biochemical interactions, we summarize the distinct roles of the CRL4 E3 ligase complexes in tumorigenesis, which appears to be tissue- and context-dependent.