The association between Salt-inducible kinase 2 (SIK2) and gamma isoform of the regulatory subunit B55 of PP2A (B55gamma) contributes to the survival of glioma cells under glucose depletion through inhibiting the phosphorylation of S6K.
The association between Salt-inducible kinase 2 (SIK2) and gamma isoform of the regulatory subunit B55 of PP2A (B55gamma) contributes to the survival of glioma cells under glucose depletion through inhibiting the phosphorylation of S6K.
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DOI：
10.1186/s12935-015-0164-6
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发表时间：
2015
影响因子：
5.8
通讯作者：
Liu JM
中科院分区：
文献类型：
--
作者：
Li YN;Cao YQ;Wu X;Han GS;Wang LX;Zhang YH;Chen X;Hao B;Yue ZJ;Liu JM
PPP2R2C编码调节亚基B55亚家族的γ同种型，其由具有A和C亚基的PP2A异源三聚体组成。目前，B55 γ在癌症中的确切功能仍在研究中。在这个项目中，我们报告了一个新的功能，B55 γ在胶质瘤细胞的葡萄糖代谢的调节。蛋白质印迹和免疫沉淀进行，以确定蛋白质的表达和相互作用。通过台盼蓝染色和使用血细胞计数器的直接细胞计数来测量细胞活力。siRNA技术用于下调蛋白表达。在胶质瘤细胞中，过表达B55 γ抑制葡萄糖摄取和乳酸产物。此外，具有更大量B55 γ的癌细胞通过S6K的去磷酸化在响应葡萄糖饥饿时显示出更高的存活优势。通过蛋白质组学分析，我们发现B55 γ通过稳定SIK2蛋白与SIK2结合并上调SIK2，这是B55 γ介导的S6K通路抑制所必需的。在B55 γ过表达细胞中敲低SIK2可恢复S6K的磷酸化。总之，我们的项目将为设计和开发针对B55 γ介导的葡萄糖代谢的治疗策略提供新的见解，用于治疗人类脑肿瘤患者。
PPP2R2C encodes a gamma isoform of the regulatory subunit B55 subfamily consisting PP2A heterotrimeric with A and C subunits. Currently, the precise functions of B55gamma in cancer are still under investigating. In this project, we reported a novel function of B55gamma in the regulation of glucose metabolism in Glioma cells. Western blot and immunoprecipitation were performed to determine protein expression and interaction. Cell viability was measured by Typan Blue staining and direct cell counting using hematocytometer. siRNA technology was used to down regulate protein expression. Glucose uptake and lactate product were suppressed by overexpression of B55gamma in Glioma cells. In addition, cancer cells with larger amount of B55gamma showed higher survival advantages in response to glucose starvation through the dephosphorylation of S6K. From proteomic analysis, we found B55gamma binds with and up regulates SIK2 through the stabilization of SIK2 protein which is required for the B55gamma-mediated suppression of S6K pathway. Knocking down of SIK2 in B55gamma over expressing cells recovered the phosphorylation of S6K. In summary, our project will provide novel insight into the design and development of therapeutic strategies to target the B55gamma-mediated glucose metabolism for the treatment of human brain tumor patients.
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鉴定PP2A复合物和参与细胞转化的途径。
影响因子：
11.2
作者：
Sablina AA;Hector M;Colpaert N;Hahn WC
通讯作者：
Hahn WC
影响因子：
9.9
作者：
Gaglio, Daniela;Metallo, Christian M.;Chiaradonna, Ferdinando
通讯作者：
Chiaradonna, Ferdinando
DOI：
10.1016/j.bbrc.2009.05.082
发表时间：
2009-08-07
影响因子：
3.1
作者：
Bae, Dongsoon;Ceryak, Susan
通讯作者：
Ceryak, Susan
DOI：
10.1152/ajpregu.00676.2009
发表时间：
2010-12-01
影响因子：
2.8
作者：
Du, Y.;Kowluru, A.;Kern, T. S.
通讯作者：
Kern, T. S.
影响因子：
4.8
作者：
Abraham, D;Podar, K;Baccarini, M
通讯作者：
Baccarini, M