The conformation change and tumor suppressor role of Merlin are both independent of Serine 518 phosphorylation
The conformation change and tumor suppressor role of Merlin are both independent of Serine 518 phosphorylation
复制标题
Merlin 的构象变化和抑癌作用均独立于丝氨酸 518 磷酸化
DOI：
10.1016/j.bbrc.2017.09.077
复制
发表时间：
2017
影响因子：
3.1
通讯作者：
Zhou Hao
中科院分区：
文献类型：
--
作者：
Xing Wancai;Li Meng;Zhang Fayou;Ma Xing;Long Jiafu;Zhou Hao
Merlin作为肿瘤抑制因子发挥作用，通过多种机制抑制癌细胞的恶性活动。然而，丝氨酸518磷酸化是否调节Merlin的构象以及开-闭构象变化是否影响Merlin的肿瘤抑制活性仍然存在争议。在这项研究中，我们使用不同的突变体来模拟梅林的相关构象状态，并研究其生理功能。我们的研究结果表明，丝氨酸518磷酸化对Merlin的构象，亚细胞定位或细胞增殖抑制活性没有影响。作为完全闭合的构象状态，A585 W突变体丧失了将Lats 2募集到细胞膜的能力，但不影响其亚细胞分布或细胞增殖抑制活性。作为一种完全开放的构象状态，模拟Merlin亚型II的构象，ΔEL突变体具有与野生型Merlin亚型I相同的生理功能。总的来说，我们第一次提供了活体证据表明，梅林的功能，作为一种肿瘤抑制剂是独立的构象变化。
Merlin functions as a tumor suppressor and suppresses malignant activity of cancer cells through multiple mechanisms. However, whether Serine 518 phosphorylation regulates the conformation of Merlin as well as the open-closed conformational changes affect Merlin's tumor inhibitory activity remain controversial. In this study, we used different mutants to mimic related conformational states of Merlin and investigated its physiological functions. Our results showed that the phosphorylation at Serine 518 has no influence on Merlin's conformation, subcellular localization, or cell proliferation inhibitory activity. As a fully closed conformational state, the A585W mutant loses the ability to recruit Lats2 to the cell membrane, but it does not affect its subcellular distribution or cell proliferation inhibitory activity. As a fully open conformational state, mimicking the conformation of Merlin isoform II, the ΔEL mutant has the same physiological function as the wild type Merlin isoform I. Collectively, we provide for the first time invivoevidence that the function of Merlin, as a tumor suppressor is independent of its conformational change.