AMOT is required for YAP function in high glucose induced liver malignancy
AMOT is required for YAP function in high glucose induced liver malignancy
复制标题
AMOT 是高糖诱导的肝脏恶性肿瘤中 YAP 功能所必需的
DOI：
10.1016/j.bbrc.2017.12.010
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发表时间：
2018
影响因子：
3.1
通讯作者：
Sun Fenyong
中科院分区：
文献类型：
--
作者：
Liu Ya;Lu Zhicheng;Shi Yi;Sun Fenyong
AMOT已被确定为雅普相互作用者。然而，AMOT如何调节雅普仍不清楚，存在争议。在此，我们发现除了雅普，AMOT是另一个Hippo信号核心因子，其可以被O-GlcNAc酰化。此外，高糖（HG）能够增强AMOT的表达和O-GlcNAc化。HG通过AMOT促进雅普的核积累、转录活性、与转录因子的相互作用以及靶基因的转录，而在正常葡萄糖水平下，AMOT对雅普起抑制作用。最后，我们观察了链脲佐菌素（STZ）诱导的高糖小鼠中AMOT和雅普的上调和核积聚。总的来说，我们已经发现AMOT在高葡萄糖水平下充当雅普刺激剂。针对Hippo通路中异常调节的核心因子可能是治疗可能合并糖尿病的肝癌的一种更有效的方法。
AMOT has been identified as a YAP interactor. However, how AMOT regulates YAP remains unclear and controversy. Here, we identified that besides YAP, AMOT was another Hippo signaling core factor which could be O-GlcNAcylated. Moreover, high glucose (HG) was able to enhance the expression and O-GlcNAcylation of AMOT. We also found that HG stimulated nuclear accumulation, transcription activity, interaction with transcription factor and transcription of target genes of YAP via AMOT, while AMOT acted as a suppressor of YAP in normal glucose level. Finally, we observed the upregulation and nuclear accumulation of AMOT and YAP in Streptozocin (STZ) induced high glucose mice. Collectively, we have uncovered that AMOT acts as a YAP stimulator in high glucose level. Targeting the aberrantly regulated core factors in Hippo pathway might be a more effective therapeutic approach for liver cancer associated with possibly diabetes.