Ilsong Institute of Life Science, Hallym University, Ahnyang, Gyeonggi-do, South Korea.
Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Kangwon-do, Republic of Korea.
Small GTPases. 2020 Mar;11(2):95-102. doi: 10.1080/21541248.2017.1364831. Epub 2017 Dec 3.
Rho GTPases play significant roles in cellular function and their activity is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), providing activation and inactivation of these GTPases, respectively. Active GTP-bound form of RhoA activates its effector proteins while the inactive GDP-bound form of RhoA exists in a RhoA-RhoGDI (guanine nucleotide dissociation inhibitor) complex in the cytosol. In particular, IκB kinase γ IKKγ/NF-κB essential modulator (NEMO) plays a role as a GDI displacement factor (GDF) for RhoA activation through binding to RhoA-RhoGDI complex. Meanwhile, prion protein inactivates RhoA despite RhoA/RhoGDI association. Novel target proteins for Rho-associated kinase (ROCK) such as glycogen synthase kinase (GSK)-3β and IKKβ are recently discovered. Here, we elaborate on a post-translationally modified version of RhoA, phosphorylated at Tyr42 and oxidized at Cys16/20. This form of RhoA dissociates from RhoA-RhoGDI complex and activates IKKβ on IKKγ/NEMO, thus providing possibly a critical role for tumourigenesis.
Rho GTPases 在细胞功能中发挥重要作用，其活性受鸟嘌呤核苷酸交换因子（GEFs）和 GTPase 激活蛋白（GAPs）调节，分别提供这些 GTPases 的激活和失活。RhoA 的活性 GTP 结合形式激活其效应蛋白，而无活性的 GDP 结合形式的 RhoA 存在于细胞质中的 RhoA-RhoGDI（鸟嘌呤核苷酸解离抑制剂）复合物中。特别是，IκB 激酶 γ（IKKγ）/NF-κB 必需调节剂（NEMO）作为 RhoA 激活的 GDI 置换因子（GDF），通过与 RhoA-RhoGDI 复合物结合发挥作用。同时，朊病毒蛋白尽管与 RhoA/RhoGDI 结合，但会使 RhoA 失活。最近发现了 Rho 相关激酶（ROCK）的新靶蛋白，如糖原合酶激酶（GSK）-3β和 IKKβ。在这里，我们详细介绍了 RhoA 的一种翻译后修饰形式，即 Tyr42 磷酸化和 Cys16/20 氧化的 RhoA。这种形式的 RhoA 从 RhoA-RhoGDI 复合物中解离出来，并在 IKKγ/NEMO 上激活 IKKβ，从而为肿瘤发生提供了可能的关键作用。
