CUL3编码泛素连接酶E3复合物的一个组分，共价连接泛素到目标识别的蛋白，用于26S蛋白酶体进行随后的靶蛋白降解。含有BTB蛋白-蛋白相互作用结构域的蛋白将降解靶标募集到含有CUL3的泛素连接酶E3复合物中以降解。CUL3也参与了与溶酶体降解相关的内涵体的成熟，而CUL3的消耗会影响溶酶体的运输。CUL3的突变也与II型假性醛固酮增多症有关。含有BTB结构域的代表蛋白KEAP1，它将氧化应激信号因子NRF2募集到含有CUL3的泛素连接酶E3复合物中进行降解。有研究显示，NRF2，KEAP1和CUL3上的突变会破坏KEAP1的降解，并随后通过KEAP1和NRF2上调氧化应激反应并增强肿瘤的存活。但是目前在癌症中CUL3突变比例比较低。

CUL3 encodes a component of the E3-ubiquitin ligase complex, which covalently attaches ubiquitin to target identified proteins for subsequent target degradation by the 26S proteasome. Proteins containing the BTB protein-protein interaction domain recruit degradation targets to the CUL3-containing E3-ubiquitin ligase complex for degradation. CUL3 is also involved in the maturation of endosomes associated with lysosomal degradation, and depletion of CUL3 has been shown to impair endolysosomal trafficking. Mutations in CUL3 are also associated with type II pseudohypoaldosteronism. A prominent BTB-containing protein is KEAP1, which recruits the oxidative-stress signaling factor, NRF2, to the CUL3-containing E3-ubiquitin ligase complex for degradation. Mutations in NRF2, KEAP1, and CUL3 have been shown to disrupt the degradation of KEAP1, and subsequently, up-regulate the oxidative stress response via KEAP1 and NRF2 and enhance survival of the tumor.

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