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本文引用的文献

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RASSF proteins.RASSF蛋白
Curr Biol. 2010 Apr 27;20(8):R344-5. doi: 10.1016/j.cub.2010.02.019.
2
Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signaling.联合功能基因组学和蛋白质组学方法鉴定出一个 PP2A 复合物，它是 Hippo 信号的负调控因子。
Mol Cell. 2010 Aug 27;39(4):521-34. doi: 10.1016/j.molcel.2010.08.002.
3
Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway activity via maintenance of protein phosphatase-2A catalytic subunit levels and consequent suppression of inhibitory Raf-1 phosphorylation.哺乳动物 Ste20 样激酶 (Mst2) 通过维持蛋白磷酸酶-2A 催化亚基水平，从而抑制抑制性 Raf-1 磷酸化，间接支持 Raf-1/ERK 通路活性。
J Biol Chem. 2010 May 14;285(20):15076-15087. doi: 10.1074/jbc.M109.078915. Epub 2010 Mar 8.
4
Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver.Hippo 信号通路是哺乳动物肝脏中一种有效的体内生长和肿瘤抑制途径。
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1437-42. doi: 10.1073/pnas.0911427107. Epub 2010 Jan 4.
5
Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression.哺乳动物 Mst1 和 Mst2 激酶在器官大小控制和肿瘤抑制中发挥着重要作用。
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1431-6. doi: 10.1073/pnas.0911409107. Epub 2010 Jan 8.
6
Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene.Mst1和Mst2通过使Yap1致癌基因失活来维持肝细胞静止并抑制肝细胞癌的发展。
Cancer Cell. 2009 Nov 6;16(5):425-38. doi: 10.1016/j.ccr.2009.09.026.
7
The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation.MST1 和 hMOB1 肿瘤抑制因子通过调节 NDR 激酶磷酸化控制人类中心体复制。
Curr Biol. 2009 Nov 3;19(20):1692-702. doi: 10.1016/j.cub.2009.09.020.
8
Hippo pathway-dependent and -independent roles of RASSF6.RASSF6在Hippo信号通路依赖及非依赖过程中的作用
Sci Signal. 2009 Sep 29;2(90):ra59. doi: 10.1126/scisignal.2000300.
9
RASSF2 associates with and stabilizes the proapoptotic kinase MST2.RASSF2与促凋亡激酶MST2结合并使其稳定。
Oncogene. 2009 Aug 20;28(33):2988-98. doi: 10.1038/onc.2009.152. Epub 2009 Jun 15.
10
The DeMSTification of mammalian Ste20 kinases.哺乳动物Ste20激酶的去神秘化
Curr Biol. 2009 May 26;19(10):R421-5. doi: 10.1016/j.cub.2009.04.022.

抑癌基因 RASSF1A 可防止哺乳动物 STE20 样激酶 MST1 和 MST2 的去磷酸化。

The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2.

机构信息

Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, California 91010, USA.

出版信息

J Biol Chem. 2011 Feb 25;286(8):6253-61. doi: 10.1074/jbc.M110.178210. Epub 2011 Jan 3.

DOI:10.1074/jbc.M110.178210
PMID:21199877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3057778/
Abstract

The RASSF1A tumor suppressor protein interacts with the pro-apoptotic mammalian STE20-like kinases MST1 and MST2 and induces their autophosphorylation and activation, but the mechanism of how RASSF1A activates MST1/2 is unclear. Okadaic acid treatment and PP2A knockdown promoted MST1/2 phosphorylation. Data from dephosphorylation assays and reduced activation of MST1/2 seen after RASSF1A depletion suggest that dephosphorylation of MST1/2 on Thr-183 and Thr-180 by PP2A is prevented by RASSF1A, shifting the balance of MST1/2 to the activated autophosphorylated form. In addition to preventing dephosphorylation, RASSF1A also stabilized the MST2 protein. Through binding to MST1/2, RASSF1A supports maintenance of MST1/2 phosphorylation, promoting an active state of the MST kinases and favoring induction of apoptosis. This is one of the first examples of a tumor suppressor acting as an inhibitor of a specific dephosphorylation pathway.

摘要

RASSF1A 肿瘤抑制蛋白与促凋亡的哺乳动物 STE20 样激酶 MST1 和 MST2 相互作用，并诱导其自身磷酸化和激活，但 RASSF1A 如何激活 MST1/2 的机制尚不清楚。冈田酸处理和 PP2A 敲低促进了 MST1/2 的磷酸化。磷酸化实验数据和 RASSF1A 耗竭后观察到的 MST1/2 活性降低表明，RASSF1A 阻止了 PP2A 对 Thr-183 和 Thr-180 的 MST1/2 去磷酸化，使 MST1/2 向激活的自身磷酸化形式转变。除了防止去磷酸化，RASSF1A 还稳定了 MST2 蛋白。通过与 MST1/2 结合，RASSF1A 支持 MST1/2 磷酸化的维持，促进 MST 激酶的活性状态，并有利于诱导细胞凋亡。这是肿瘤抑制因子作为特定去磷酸化途径抑制剂的第一个例子之一。