The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals.
The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals.
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DOI：
10.1016/j.devcel.2010.06.015
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发表时间：
2010-07-20
影响因子：
11.8
通讯作者：
Pan, Duojia
中科院分区：
文献类型：
--
作者：
Zhang, Nailing;Bai, Haibo;David, Karen K.;Dong, Jixin;Zheng, Yonggang;Cai, Jing;Giovannini, Marco;Liu, Pentao;Anders, Robert A.;Pan, Duojia
保守的Hippo信号通路调节果蝇和哺乳动物的器官大小。虽然已经建立了从蛋白激酶Hippo（Hpo）（哺乳动物中的Mst 1和Mst 2）到转录共激活因子Yorkie（Yki）（哺乳动物中的雅普）的核心激酶级联，但是Hippo激酶级联的上游调节剂不太清楚，特别是在哺乳动物中。使用肝脏特异性条件性基因敲除小鼠，我们证明了Merlin/NF 2肿瘤抑制因子和雅普癌蛋白拮抗性地调节肝脏发育。雅普的失活导致肝细胞和胆管上皮细胞的丢失，而Nf 2的失活导致肝细胞癌和胆管错构瘤。引人注目的是，Nf 2缺陷型在很大程度上受到雅普杂合缺失的抑制，表明雅普是Merlin/NF 2在生长调节中的主要效应子。我们的研究将Merlin/NF 2与哺乳动物Hippo信号传导联系起来，并暗示雅普激活是与神经纤维瘤病2相关的病理学介质。
The conserved Hippo signaling pathway regulates organ size in both Drosophila and mammals. While a core kinase cascade leading from the protein kinase Hippo (Hpo) (Mst1 and Mst2 in mammals) to the transcription coactivator Yorkie (Yki) (YAP in mammals) has been established, upstream regulators of the Hippo kinase cascade are less well defined, especially in mammals. Using liver-specific conditional knockout mice, we demonstrate that the Merlin/NF2 tumor suppressor and the YAP oncoprotein function antagonistically to regulate liver development. While inactivation of Yap led to loss of hepatocytes and biliary epithelial cells, inactivation of Nf2 led to hepatocellular carcinoma and bile duct hamartoma. Strikingly, the Nf2-deficient phenotype was largely suppressed by heterozygous deletion of Yap, suggesting that YAP is a major effector of Merlin/NF2 in growth regulation. Our studies link Merlin/NF2 to mammalian Hippo signaling and implicate YAP activation as a mediator of pathologies relevant to Neurofibromatosis 2.
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影响因子：
4.6
作者：
Kango-Singh, M;Nolo, R;Halder, G
通讯作者：
Halder, G
影响因子：
9.2
作者：
Bennett, F. Christian;Harvey, Kieran F.
通讯作者：
Harvey, Kieran F.
影响因子：
11.8
作者：
Genevet A;Wehr MC;Brain R;Thompson BJ;Tapon N
通讯作者：
Tapon N
影响因子：
64.5
作者：
Harvey, KF;Pfleger, CM;Hariharan, IK
通讯作者：
Hariharan, IK
DOI：
10.1073/pnas.0911427107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Lu, Li;Li, Ying;Johnson, Randy L.
通讯作者：
Johnson, Randy L.