Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark.
Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
G3 (Bethesda). 2020 Apr 9;10(4):1319-1325. doi: 10.1534/g3.120.401038.
The Hippo pathway regulates growth and apoptosis. We identify RhoBTB proteins as novel regulators of Hippo signaling. RhoBTB depletion in the wing disc epithelium cooperated with Yki to drive hyperplasia into neoplasia. Depletion of RhoBTB2 caused elevated YAP activity in human cells. RhoBTB2 deficiency resulted in increased colony formation in assays for anchorage-independent growth. We provide evidence that RhoBTBs acts on Hippo signaling through regulation of the kinase LKB1. LKB1 protein levels were reduced upon RhoBTB2 depletion, which correlated with increased LKB1 ubiquitination. Restoring LKB1 levels rescued loss of RhoBTB in Our results suggest that RhoBTB-dependent LKB1 regulation may contribute to its tumor-suppressive function.
Hippo 通路调节生长和细胞凋亡。我们发现 RhoBTB 蛋白是 Hippo 信号通路的新型调节因子。在 wing disc 上皮细胞中敲低 RhoBTB 蛋白与 Yki 合作，将增生转化为肿瘤。RhoBTB2 的敲低导致人类细胞中 YAP 活性升高。RhoBTB2 缺失导致在非锚定依赖性生长测定中集落形成增加。我们提供的证据表明，RhoBTB 通过调节激酶 LKB1 来作用于 Hippo 信号通路。RhoBTB2 缺失后 LKB1 蛋白水平降低，这与 LKB1 泛素化增加相关。恢复 LKB1 水平可挽救 RhoBTB 的缺失。我们的结果表明，RhoBTB 依赖性 LKB1 调节可能有助于其肿瘤抑制功能。
