MOB 调控：激酶调控因子的保守家族研究
MOB control: reviewing a conserved family of kinase regulators.
机构信息
Tumour Suppressor Signalling Networks laboratory, UCL Cancer Institute, University College London, WC1E 6BT, London, United Kingdom.
出版信息
Cell Signal. 2011 Sep;23(9):1433-40. doi: 10.1016/j.cellsig.2011.04.007. Epub 2011 Apr 21.
Abstract
The family of Mps One binder (MOB) co-activator proteins is highly conserved from yeast to man. At least two different MOB proteins have been identified in every eukaryote analysed to date. Initially, yeast genetics revealed essential roles for Mob1p and Mob2p in the regulation of mitotic exit and cell morphogenesis. Studies in flies then showed that dMOB1/MATS is a core component of Hippo signalling. Loss of dMOB1 resulted in increased cell proliferation and decreased cell death, suggesting that MOB1 acts as tumour suppressor protein. Recent work focused primarily on mammalian cells has shown how hMOB1 can regulate NDR/LATS kinases, a function that can to be counteracted by hMOB2. Here we summarise and discuss our current knowledge of this emerging protein family, with emphasis on subcellular localisation, protein-protein interactions and biological functions in apoptosis, mitosis, morphogenesis, cell proliferation and centrosome duplication.
摘要
Mps One 衔接蛋白（MOB）辅激活因子家族在从酵母到人高度保守。迄今为止，分析的每种真核生物中至少鉴定出两种不同的 MOB 蛋白。最初，酵母遗传学揭示了 Mob1p 和 Mob2p 在有丝分裂退出和细胞形态发生调节中的重要作用。随后在果蝇中的研究表明，dMOB1/MATS 是 Hippo 信号的核心组成部分。dMOB1 的缺失导致细胞增殖增加和细胞死亡减少，表明 MOB1 作为肿瘤抑制蛋白发挥作用。最近主要集中在哺乳动物细胞的研究表明 hMOB1 如何调节 NDR/LATS 激酶，hMOB2 可以拮抗该功能。在这里，我们总结和讨论了我们对这个新兴蛋白家族的现有认识，重点是亚细胞定位、蛋白-蛋白相互作用以及在细胞凋亡、有丝分裂、形态发生、细胞增殖和中心体复制中的生物学功能。
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本文引用的文献
1
The promotion of neurite formation in Neuro2A cells by mouse Mob2 protein.小鼠Mob2蛋白对Neuro2A细胞中神经突形成的促进作用。
FEBS Lett. 2011 Feb 4;585(3):523-30. doi: 10.1016/j.febslet.2011.01.003. Epub 2011 Jan 14.
2
A tissue-specific atlas of mouse protein phosphorylation and expression.小鼠蛋白磷酸化和表达的组织特异性图谱。
Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
3
Primary cilium-dependent and -independent Hedgehog signaling inhibits p16(INK4A).初级纤毛依赖和独立的 Hedgehog 信号抑制 p16(INK4A)。
Mol Cell. 2010 Nov 24;40(4):533-47. doi: 10.1016/j.molcel.2010.10.027.
4
Hippo signaling at a glance.Hippo信号通路简介。
J Cell Sci. 2010 Dec 1;123(Pt 23):4001-6. doi: 10.1242/jcs.069070.
5
Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction.Hippo 通路的组成部分与 Nek2 激酶合作调节中心体分离。
Nat Cell Biol. 2010 Dec;12(12):1166-76. doi: 10.1038/ncb2120. Epub 2010 Nov 14.
6
The hippo signaling pathway in development and cancer.河马信号通路在发育和癌症中的作用。
Dev Cell. 2010 Oct 19;19(4):491-505. doi: 10.1016/j.devcel.2010.09.011.
7
A human MAP kinase interactome.一个人类 MAP 激酶相互作用组。
Nat Methods. 2010 Oct;7(10):801-5. doi: 10.1038/nmeth.1506.
8
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9
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Trends Biochem Sci. 2010 Nov;35(11):627-33. doi: 10.1016/j.tibs.2010.05.010. Epub 2010 Jul 2.
10
Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma.激酶 NDR1 的消融使小鼠易于发生 T 细胞淋巴瘤。
Sci Signal. 2010 Jun 15;3(126):ra47. doi: 10.1126/scisignal.2000681.
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