Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays important roles in numerous cellular processes, including cell motility, adhesion, and proliferation, by regulating the activity of Rho GTPases. Its expression is altered in various human cancers and is associated with malignant progression. Here, we show that RhoGDI1 interacts with Cullin 3 (CUL3), a scaffold protein for E3 ubiquitin ligase complexes. Ectopic expression of CUL3 increases the ubiquitination of RhoGDI1. Furthermore, potassium channel tetramerization domain containing 5 (KCTD5) also binds to RhoGDI1 and increases its interaction with CUL3. Ectopic expression of KCTD5 increases the ubiquitination of RhoGDI1, whereas its knockdown by RNA interference has the opposite effect. Depletion of KCTD5 or expression of dominant-negative CUL3 (DN-CUL3) enhances the stability of RhoGDI1. Our findings reveal a previously unknown mechanism for controlling RhoGDI1 degradation that involves a CUL3/KCTD5 ubiquitin ligase complex.

中文翻译：

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Cullin 3/KCTD5 促进 Rho 鸟嘌呤核苷酸解离抑制剂 1 的泛素化并调节其稳定性。

Rho 鸟嘌呤核苷酸解离抑制剂 1 (RhoGDI1) 通过调节 Rho GTP 酶的活性在许多细胞过程中发挥重要作用，包括细胞运动、粘附和增殖。它的表达在各种人类癌症中发生改变，并与恶性进展有关。在这里，我们显示 RhoGDI1 与 Cullin 3 (CUL3) 相互作用，Cullin 3 (CUL3) 是 E3 泛素连接酶复合物的支架蛋白。CUL3 的异位表达增加了 RhoGDI1 的泛素化。此外，钾通道四聚结构域 5 (KCTD5) 也与 RhoGDI1 结合并增加其与 CUL3 的相互作用。KCTD5 的异位表达增加了 RhoGDI1 的泛素化，而通过 RNA 干扰将其敲低具有相反的效果。KCTD5 的消耗或显性失活 CUL3 (DN-CUL3) 的表达增强了 RhoGDI1 的稳定性。我们的研究结果揭示了一种以前未知的控制 RhoGDI1 降解的机制，该机制涉及 CUL3/KCTD5 泛素连接酶复合物。