PPP1R12A是一种循环内体酸酶,可促进YAP激活
Chiaki Inoue1, Kojiro Mukai2, Tatsuyuki Matsudaira1
1Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Scientific reports
|November 13, 2023
概括
研究人员在回收内分泌体中发现了一种新型的"ATP8A1-脂-YAP酸酶"轴,该轴驱动癌细胞增殖. 这条涉及PPP1R12A的途径对于YAP激活至关重要,并且与乳腺癌预后不佳相关.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 是的相关蛋白 (YAP) 是一个关键的转录协活性剂,驱动癌症恶性.
- 在回收内分泌体 (RE) 中,YAP活性受到脂素 (PS) 的积极调节,但确切的机制尚不清楚.
研究的目的:
- 阐明在RES中由PS激活YAP的机制.
- 确定参与PSYYAP激活的酸酶.
主要方法:
- 对候选酸盐酶的淘汰实验.
- 对YAP酸化和核定位的分析.
- 亚细胞分离. 亚细胞分离.
- 与癌症基因组图谱 (TCGA) 数据的相关性分析.
主要成果:
- PPP1R12A是肌酸酸酶的一个子单元,对于三阴性乳腺癌细胞中依赖于YAP的增殖至关重要.
- 抑制PPP1R12A增加了YAP酸化,减少了核YAP,并抑制了CTGF转录.
- 由于ATP8A1的耗尽,PPP1R12A从微小的部分转移到细胞质的部分.
- PP1R12A,PP1B或ATP8A1的高表达与乳腺癌预后不佳相关.
结论:
- 在RE中的ATP8A1-PS-YAP酸酶轴促进了YAP的激活,并促进了癌细胞的增殖.
- PPP1R12A和ATP8A1是乳腺癌的潜在治疗点.
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