β-Arrestin1 promotes the progression of chronic myeloid leukaemia by regulating BCR/ABL H4 acetylation.
β-Arrestin1 promotes the progression of chronic myeloid leukaemia by regulating BCR/ABL H4 acetylation.
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beta-Arrestin1通过调节BCR/ABL H4乙酰化促进慢性粒细胞白血病的进展
DOI：
10.1038/bjc.2014.335
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发表时间：
2014-07-29
影响因子：
8.8
通讯作者：
Zou L
中科院分区：
文献类型：
--
作者：
Qin R;Li K;Qi X;Zhou X;Wang L;Zhang P;Zou L
β-Arrestins是与各种细胞信号相互作用的支架蛋白。尽管β-arrestin 2介导了髓系白血病的发生和发展，但β-arrestin 1在慢性髓系白血病（CML）中的作用尚不清楚。本研究旨在探讨β-arrestin 1在慢性粒细胞白血病（CML）中的作用。采用RT-PCR、免疫荧光和Western blotting方法检测CML患者、动物模型及K562细胞中β-arrestin 1和BCR/ABL的表达。采用集落形成实验、MTT法和细胞存活分析等方法，观察β-arrestin 1对CML动物模型和K562细胞的影响。BCR/ABL H4乙酰化通过使用Chromatin-免疫沉淀（ChIP）-芯片分析并分别通过ChIP确认。免疫共沉淀和共聚焦检测β-arrestin 1与zeste同源物增强子2（EZH 2）的结合。β-arrestin 1的高表达与CML患者的临床分期呈正相关。β-arrestin 1的消耗减缓K562和原代细胞的进展，并增加CML小鼠的存活率。重要的是，沉默的β-arrestin 1导致K562细胞中BCR/ABL H4乙酰化水平的降低。进一步的数据表明，核β-arrestin 1与EZH 2结合，介导BCR/ABL乙酰化，从而调节K562细胞中的细胞进展和CML小鼠的存活。我们的研究结果揭示了β-arrestin 1与EZH 2结合的新功能，通过调节BCR/ABL H4乙酰化促进CML进展。
β-Arrestins are scaffold proteins that interact with various cellular signals. Although β-arrestin2 mediates the initiation and progression of myeloid leukaemia, the critical role of β-arrestin1 in the chronic myeloid leukaemia (CML) is still unknown. The aim of this study is to investigate the essential function of β-arrestin1 in CML. The expressions of β-arrestin1 and BCR/ABL in CML patients, animal models and K562 cells were measured by RT–PCR, immunofluorescence and western blotting. The effect of β-arrestin1 on CML animal models and K562 cells by colony formation, MTT and survival analysis were assessed. BCR/ABL H4 acetylation was analysed through the use of Chromatin-immunoprecipitation (ChIP) -on-chip and confirmed by ChIP respectively. Co-immunoprecipitation and confocal were examined for the binding of β-arrestin1 with enhancer of zeste homologue 2 (EZH2). The higher expression of β-arrestin1 is positively correlated with clinical phases of CML patients. Depletion of β-arrestin1 decelerates progression of K562 and primary cells, and increases survival of CML mice. Importantly, silenced β-arrestin1 results in the decrease of BCR/ABL H4 acetylation level in K562 cells. Further data illustrate that nuclear β-arrestin1 binds to EZH2 to mediate BCR/ABL acetylation and thus regulates cell progression in K562 cells and the survival of CML mice. Our findings reveal a novel function of β-arrestin1 binding to EZH2 to promote CML progression by regulating BCR/ABL H4 acetylation.
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影响因子：
4.8
作者：
Ge, L;Shenoy, SK;DeFea, K
通讯作者：
DeFea, K
影响因子：
50.3
作者：
Neviani, P;Santhanam, R;Perrotti, D
通讯作者：
Perrotti, D
体细胞突变改变生发中心起源的滤泡性和弥漫性大 B 细胞淋巴瘤中的 EZH2 (Tyr641)。
影响因子：
30.8
作者：
Morin, Ryan D.;Johnson, Nathalie A.;Severson, Tesa M.;Mungall, Andrew J.;An, Jianghong;Goya, Rodrigo;Paul, Jessica E.;Boyle, Merrill;Woolcock, Bruce W.;Kuchenbauer, Florian;Yap, Damian;Humphries, R. Keith;Griffith, Obi L.;Shah, Sohrab;Zhu, Henry;Kimbara, Michelle;Shashkin, Pavel;Charlot, Jean F.;Tcherpakov, Marianna;Corbett, Richard;Tam, Angela;Varhol, Richard;Smailus, Duane;Moksa, Michelle;Zhao, Yongjun;Delaney, Allen;Qian, Hong;Birol, Inanc;Schein, Jacqueline;Moore, Richard;Holt, Robert;Horsman, Doug E.;Connors, Joseph M.;Jones, Steven;Aparicio, Samuel;Hirst, Martin;Gascoyne, Randy D.;Marra, Marco A.
通讯作者：
Marra, Marco A.
影响因子：
30.5
作者：
Su, IH;Basavaraj, A;Tarakhovsky, A
通讯作者：
Tarakhovsky, A
影响因子：
6.4
作者：
Jia, Ling-Fei;Wei, Su-Bi;Yu, Guang-Yan
通讯作者：
Yu, Guang-Yan