Protein Palmitoylation Regulates Cell Survival by Modulating XBP1 Activity in Glioblastoma Multiforme.
Protein Palmitoylation Regulates Cell Survival by Modulating XBP1 Activity in Glioblastoma Multiforme.
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蛋白质棕榈酰化通过调节多形性胶质母细胞瘤中的 XBP1 活性来调节细胞存活
DOI：
10.1016/j.omto.2020.05.007
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发表时间：
2020-06-26
期刊：
影响因子：
--
通讯作者：
Fang Z
中科院分区：
文献类型：
--
作者：
Chen X;Li H;Fan X;Zhao C;Ye K;Zhao Z;Hu L;Ma H;Wang H;Fang Z
多形性胶质母细胞瘤（GBM）几乎总是获得侵袭性表型，导致有限的治疗选择。蛋白棕榈酰化显著影响GBM的肿瘤发生和恶性进展。然而，蛋白棕榈酰化在GBM中的作用尚未有系统的报道。本研究旨在探讨蛋白棕榈酰化对GBM细胞存活及细胞周期的影响。在本研究中，大多数棕榈酰转移酶在GBM及其细胞系中上调，蛋白棕榈酰化参与了控制细胞存活和GBM细胞周期的信号通路。底物类似物抑制剂抑制蛋白棕榈酰化，即2-溴铝酸盐、蓝绿蛋白和tunicamycin，通过增强内质网（ER）应激诱导GBM细胞G2细胞周期阻滞和细胞死亡。这些作用主要归因于棕榈酰化抑制剂激活促凋亡途径和内质网应激信号。进一步的分析显示，summoylated XBP1 （X-box结合蛋白1）的积累及其转录抑制，以及XBP1棕榈酰化的减少。综上所述，目前的结果表明，蛋白棕榈酰化在GBM细胞的存活中起着重要作用，进一步为GBM提供了潜在的治疗策略。蛋白棕榈酰化通过抑制XBP1的SUMOylation并激活其转录功能，在GBM细胞的细胞存活和细胞周期中发挥重要作用。
Glioblastoma multiforme (GBM) almost invariably acquires an invasive phenotype, resulting in limited therapeutic options. Protein palmitoylation markedly affects tumorigenesis and malignant progression in GBM. The role of protein palmitoylation in GBM, however, has not been systematically reported. This study aimed to investigate the effect of protein palmitoylation on GBM cell survival and the cell cycle. In this study, most palmitoyltransferases were upregulated in GBM and its cell lines, and protein palmitoylation participated in signaling pathways controlling cell survival and the GBM cell cycle. Inhibition of protein palmitoylation with substrate-analog inhibitors, that is, 2-bromopalmitate, cerulenin, and tunicamycin, induced G2 cell cycle arrest and cell death in GBM cells through enhanced endoplasmic reticulum (ER) stress. These effects are primarily attributed to the palmitoylation inhibitors activating pro-apoptotic pathways and ER stress signals. Further analysis revealed was the accumulation of SUMOylated XBP1 (X-box binding protein 1) and its transcriptional repression, along with a reduction in XBP1 palmitoylation. Taken together, the present results indicate that protein palmitoylation plays an important role in the survival of GBM cells, further providing a potential therapeutic strategy for GBM. Protein palmitoylation plays an important role in the cell survival and cell cycle of GBM cells through the suppression of XBP1’s SUMOylation and the activation of its transcriptional function.
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在条件X-box结合蛋白-1（XBP1）敲除小鼠中，从肝胰岛素抵抗中从肝胰岛素抵抗中解离肌醇提取酶（IRE1α）介导的C-JUN N末端激酶激活。
DOI：
10.1074/jbc.m111.316760
发表时间：
2012-01-20
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jurczak MJ;Lee AH;Jornayvaz FR;Lee HY;Birkenfeld AL;Guigni BA;Kahn M;Samuel VT;Glimcher LH;Shulman GI
通讯作者：
Shulman GI
影响因子：
4
作者：
Brown M;Strudwick N;Suwara M;Sutcliffe LK;Mihai AD;Ali AA;Watson JN;Schröder M
通讯作者：
Schröder M
影响因子：
4.6
作者：
Kishino A;Hayashi K;Hidai C;Masuda T;Nomura Y;Oshima T
通讯作者：
Oshima T
DOI：
10.1111/febs.14608
发表时间：
2019-01
期刊：
The FEBS journal
影响因子：
--
作者：
Almanza A;Carlesso A;Chintha C;Creedican S;Doultsinos D;Leuzzi B;Luís A;McCarthy N;Montibeller L;More S;Papaioannou A;Püschel F;Sassano ML;Skoko J;Agostinis P;de Belleroche J;Eriksson LA;Fulda S;Gorman AM;Healy S;Kozlov A;Muñoz-Pinedo C;Rehm M;Chevet E;Samali A
通讯作者：
Samali A
影响因子：
3.7
作者：
Nicolao MC;Loos JA;Rodriguez Rodrigues C;Beas V;Cumino AC
通讯作者：
Cumino AC