Donninger Howard, Schmidt M Lee, Mezzanotte Jessica, Barnoud Thibaut, Clark Geoffrey J
Department of Medicine, University of Louisville, KY, 40202, USA.
Department of Pharmacoloxy and Toxicology, University of Louisville, KY, 40202, USA.
Semin Cell Dev Biol. 2016 Oct;58:86-95. doi: 10.1016/j.semcdb.2016.06.007. Epub 2016 Jun 8.
There are six core RASSF family proteins that contain conserved Ras Association domains and may serve as Ras effectors. They lack intrinsic enzymatic activity and appear to function as scaffolding and localization molecules. While initially being associated with pro-apoptotic signaling pathways such as Bax and Hippo, it is now clear that they can also connect Ras to a surprisingly broad range of signaling pathways that control senescence, inflammation, autophagy, DNA repair, ubiquitination and protein acetylation. Moreover, they may be able to impact the activation status of pro-mitogenic Ras effector pathways, such as the Raf pathway. The frequent epigenetic inactivation of RASSF genes in human tumors disconnects Ras from pro-death signaling systems, enhancing Ras driven transformation and metastasis. The best characterized members are RASSF1A and RASSF5 (NORE1A).
有六种核心RASSF家族蛋白，它们含有保守的Ras关联结构域，可能作为Ras效应器。它们缺乏内在的酶活性，似乎起着支架和定位分子的作用。虽然最初与促凋亡信号通路如Bax和Hippo相关，但现在很清楚它们还能将Ras连接到一系列令人惊讶的广泛信号通路，这些通路控制衰老、炎症、自噬、DNA修复、泛素化和蛋白质乙酰化。此外，它们可能能够影响促有丝分裂Ras效应器通路（如Raf通路）的激活状态。人类肿瘤中RASSF基因频繁的表观遗传失活使Ras与促死亡信号系统断开连接，增强了Ras驱动的转化和转移。最具特征的成员是RASSF1A和RASSF5（NORE1A）。
