PDF(Pubmed)
Abstract：
RhoU is an atypical member of the Rho family of small G-proteins, which has N- and C-terminal extensions compared to the classic Rho GTPases RhoA, Rac1 and Cdc42, and associates with membranes through C-terminal palmitoylation rather than prenylation. RhoU mRNA expression is upregulated in prostate cancer and is considered a marker for disease progression. Here, we show that RhoU overexpression in prostate cancer cells increases cell migration and invasion. To identify RhoU targets that contribute to its function, we found that RhoU homodimerizes in cells. We map the region involved in this interaction to the C-terminal extension and show that C-terminal palmitoylation is required for self-association. Expression of the isolated C-terminal extension reduces RhoU-induced activation of p21-activated kinases (PAKs), which are known downstream targets for RhoU, and induces cell morphological changes consistent with inhibiting RhoU function. Our results show for the first time that the activity of a Rho family member is stimulated by self-association, and this is important for its activity.
摘要：
RhoU是小G蛋白Rho家族的非典型成员，与经典的RhoGTPasesRhoA相比，它具有N端和C端延伸，Rac1和Cdc42，并通过C端棕榈酰化而不是异戊二烯化与膜缔合。RhoUmRNA表达在前列腺癌中上调，被认为是疾病进展的标志。在这里，我们表明前列腺癌细胞中RhoU过表达增加了细胞迁移和侵袭。为了确定有助于其功能的RhoU靶标，我们发现RhoU在细胞中同源二聚体化。我们将参与这种相互作用的区域映射到C末端延伸，并显示C末端棕榈酰化是自缔合所必需的。分离的C-末端延伸的表达减少了RhoU诱导的PAKs活化，它们是RhoU已知的下游目标，并诱导与抑制RhoU功能一致的细胞形态变化。我们的研究结果首次表明，一个Rho家族成员的活动是通过自我联想来刺激的，这对它的活动很重要。
