PCAF-mediated Akt1 acetylation enhances the proliferation of human glioblastoma cells
PCAF-mediated Akt1 acetylation enhances the proliferation of human glioblastoma cells
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PCAF 介导的 Akt1 乙酰化增强人胶质母细胞瘤细胞的增殖
DOI：
10.1007/s13277-014-2522-8
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发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Shi，Lei
中科院分区：
文献类型：
--
作者：
Zhang，Shuguang;Sun，Guan;Shi，Lei
胶质母细胞瘤是人类最具侵袭性的恶性原发性脑肿瘤。PI 3 K/Akt 1信号通路的激活参与了胶质母细胞瘤的增殖，但Akt 1在胶质母细胞瘤发生发展过程中的潜在机制尚不清楚。近年来，在蛋白质水平上对分子进行修饰，如乙酰化修饰，已被证明与这些分子的功能有关。因此，本研究探讨了Akt 1分子乙酰化修饰及其在胶质母细胞瘤细胞增殖中的作用。结果显示，与正常人星形胶质细胞相比，胶质母细胞瘤细胞中的Akt 1显著乙酰化。在机制上，PCAF介导的Akt 1乙酰化增强了Akt 1在Thr 308和Ser 473两个位点的磷酸化，并进一步促进胶质母细胞瘤细胞的增殖。总之，这些数据暗示，作为一种翻译后调节，PCAF介导的Akt 1乙酰化在人类胶质母细胞瘤的增殖中起着重要的作用，这为临床应用提供了一个新的靶点。
Glioblastoma is the most aggressive malignant primary brain tumor in humans. The activation of PI3K/Akt1 signaling pathway is involved in the proliferation of glioblastoma; however, the underlying mechanism of Akt1 activation during the development of glioblastoma remains largely unclear. Recently, the modification of molecular molecules at protein level such as acetylation has been shown to be related to the function of these molecules. Thus, in our present studies, the acetylation of Akt1 molecule and its role in the proliferation of glioblastoma cells was explored. The results showed that Akt1 was markedly acetylated in glioblastoma cells compared to normal human astrocytes. Mechanistically, PCAF-mediated Akt1 acetylation enhanced Akt1 phosphorylation at both sites of Thr308and Ser473and further promoted the proliferation of glioblastoma cells. Together, these data implicate that, as a post-translational regulation, PCAF-mediated Akt1 acetylation plays an important role in the proliferation of human glioblastoma, suggesting a novel target for clinical application.