Cullin's encode the structural components for one of the most abundant E3 ubiquitin ligase families in eukaryotes accounting for as many as 400 distinct E3 ubiquitin ligases. Because of their modular assembly involving combinations of multiple distinct adaptor and substrate receptor proteins, it comes as no surprise that these E3's are implicated in a plethora of fundamental biochemical processes ranging from DNA replication and repair to transcription and development. Herein, we focus on one member of the cullin family, namely the Cullin 4-RING E3 ligases (CRL4's). More specifically, we overview what has been learned about some of the functions of CRL4's from various model systems. We discuss the unexpected association of defective CUL4B with syndromal X-linked mental retardation in humans and speculate on the biochemical consequences and clinical implications of defective CRL4 function. In particular, mutations in CUL4B highlight a previously unappreciated role for CRL4's in neuronal function and cognition in humans.

中文翻译：

---

人类 CUL4B 缺陷：了解库林 4-RING E3 泛素连接酶功能受损的临床后果。

Cullin's 编码真核生物中最丰富的 E3 泛素连接酶家族之一的结构成分，占多达 400 种不同的 E3 泛素连接酶。由于它们的模块化组装涉及多种不同的接头和底物受体蛋白的组合，因此这些 E3 涉及从 DNA 复制和修复到转录和发育的大量基本生化过程也就不足为奇了。在此，我们关注 cullin 家族的一个成员，即 Cullin 4-RING E3 连接酶 (CRL4)。更具体地说，我们概述了从各种模型系统中学到的有关 CRL4 的一些功能的知识。我们讨论了有缺陷的 CUL4B 与人类综合征 X 连锁智力低下的意外关联，并推测了有缺陷的 CRL4 功能的生化后果和临床意义。特别是，CUL4B 中的突变突出了 CRL4 在人类神经元功能和认知中以前未被重视的作用。