Regulation of deleted in liver cancer 1 tumor suppressor by protein-protein interactions and phosphorylation
Regulation of deleted in liver cancer 1 tumor suppressor by protein-protein interactions and phosphorylation
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DOI：
10.1002/ijc.28505
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发表时间：
2014-07-15
影响因子：
6.4
通讯作者：
Ping Yam, Judy Wai
中科院分区：
文献类型：
--
作者：
Ko, Frankie Chi Fat;Ping Yam, Judy Wai
肝癌缺失 1 (DLC1) 肿瘤抑制因子是一种重要的 RhoGTP 激活蛋白 (RhoGAP)，在多种人类癌症中发挥着至关重要的作用。小 GTP 酶调节正常的细胞过程，但 GTP 酶的异常表达和激活会导致肿瘤发生。 RhoGAP 抑制 Rho 活性。 DLC1 的 RhoGAP 活性和粘着斑定位对于 DLC1 的肿瘤抑制功能至关重要。 DLC1 频繁表达不足在人类癌症中很常见，可归因于基因组缺失和表观遗传失活。体细胞突变已被证明会解除 DLC1 的 RhoGAP 活性。细胞中 DLC1 的失调会导致活性 Rho 升高。对 DLC1 作用分子机制的引人注目的研究已经确定了 DLC1 的各种相互作用伙伴，例如张力蛋白和 Caveolin-1，并揭示了相关的信号传导途径。 DLC1 已被证明是一种混杂的相互作用蛋白。最近的兴趣还集中在 DLC1 的磷酸化上。 PKA、PKB/Akt 和 PKC 等上游激酶以及磷酸化对 DLC1 生物活性的影响已得到证实。尽管 DLC1 是 RhoGAP，但 RhoGAP 独立途径已通过其相互作用伙伴和磷酸化调节参与其中。最近对 DLC1 的研究指出了它所调节的信号通路的复杂性。本综述总结了目前对 DLC1 相互作用电位和 DLC1 磷酸化的理解。
The deleted in liver cancer 1 (DLC1) tumor suppressor is an important RhoGTP activating protein (RhoGAP) that plays a crucial role in many types of human cancers. Small GTPases regulate normal cellular processes but aberrant expression and activation of GTPases contribute to tumorigenesis. RhoGAP suppresses Rho activity. DLC1's RhoGAP activity and the focal adhesion localization are critical to the tumor suppressor functions of DLC1. Frequent DLC1 underexpression is commonly seen in human cancers and has been ascribed to genomic deletion and epigenetic inactivation. Somatic mutation has been shown to deregulate the RhoGAP activity of DLC1. Deregulation of DLC1 in cells results in the elevation of active Rho. Compelling studies of the molecular mechanisms of DLC1 action have identified various interacting partners of DLC1 such as tensins and caveolin-1, and revealed the associated signaling pathways. DLC1 has been shown to be a promiscuous interacting protein. Recent interest has also focused on the phosphorylation of DLC1. The upstream kinases such as PKA, PKB/Akt and PKC, and the effects of phosphorylation on the biological activities of DLC1 have been demonstrated. Although DLC1 is a RhoGAP, RhoGAP-independent pathways have been involved via its interacting partners and upon phosphorylation regulation. Recent studies of DLC1 point to the complexity of the signaling pathways it regulates. This review summarizes the current understanding of the interacting potentials of DLC1 and phosphorylation of DLC1.