依米丁通过一种依赖蛋白磷酸酶1的机制调节Bcl-x的可变剪接。
Emetine regulates the alternative splicing of Bcl-x through a protein phosphatase 1-dependent mechanism.
作者信息
Boon-Unge Kritsanapol, Yu Qingming, Zou Tie, Zhou An, Govitrapong Piyarat, Zhou Jianhua
机构信息
Department of Medicine, Program in Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
出版信息
Chem Biol. 2007 Dec;14(12):1386-92. doi: 10.1016/j.chembiol.2007.11.004.
Abstract
Exon 2 of the Bcl-x gene undergoes alternative splicing in which the Bcl-xS splice variant promotes apoptosis in contrast to the anti-apoptotic splice variant Bcl-xL. In this study, the regulation of the alternative splicing of pre-mRNA of Bcl-x was examined in response to emetine. Treatment of different types of cancer cells with emetine dihydrochloride downregulated the level of Bcl-xL mRNA with a concomitant increase in the mRNA level of Bcl-xS in a dose- and time-dependent manner. Pretreatment with calyculin A, an inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), blocked emetine-induced alternative splicing in contrast to okadaic acid, a specific inhibitor of PP2A in cells, demonstrating a PP1-mediated mechanism. Our finding on the regulation of RNA splicing of members of the Bcl-2 family in response to emetine presents a potential target for cancer treatment.
摘要
Bcl-x基因的外显子2发生可变剪接，其中Bcl-xS剪接变体促进细胞凋亡，这与抗凋亡剪接变体Bcl-xL相反。在本研究中，研究了Bcl-x前体mRNA可变剪接在应对依米丁时的调控情况。用盐酸依米丁处理不同类型的癌细胞，以剂量和时间依赖性方式下调Bcl-xL mRNA水平，同时伴随Bcl-xS mRNA水平的增加。用花萼海绵诱癌素A（一种蛋白磷酸酶1（PP1）和蛋白磷酸酶二磷酸酶2A（PP2A）的抑制剂）预处理，与冈田酸（一种细胞中PP2A的特异性抑制剂）相反，可阻断依米丁诱导的可变剪接，证明了一种PP1介导的机制。我们关于Bcl-2家族成员RNA剪接在应对依米丁时的调控的发现为癌症治疗提供了一个潜在靶点。
相似文献
1
Emetine regulates the alternative splicing of Bcl-x through a protein phosphatase 1-dependent mechanism.依米丁通过一种依赖蛋白磷酸酶1的机制调节Bcl-x的可变剪接。
Chem Biol. 2007 Dec;14(12):1386-92. doi: 10.1016/j.chembiol.2007.11.004.
2
De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1.新生神经酰胺调节A549肺腺癌细胞中半胱天冬酶9和Bcl-x的可变剪接。对蛋白磷酸酶-1的依赖性。
J Biol Chem. 2002 Apr 12;277(15):12587-95. doi: 10.1074/jbc.M112010200. Epub 2002 Jan 18.
3
Emetine and the alternative splicing of Bcl-X: where to next?依米丁与Bcl-X的可变剪接：下一步何去何从？
Chem Biol. 2007 Dec;14(12):1313-4. doi: 10.1016/j.chembiol.2007.12.002.
4
Homoharringtonine regulates the alternative splicing of Bcl-x and caspase 9 through a protein phosphatase 1-dependent mechanism.高三尖杉酯碱通过蛋白磷酸酶 1 依赖的机制调节 Bcl-x 和 caspase 9 的选择性剪接。
BMC Complement Altern Med. 2018 May 22;18(1):164. doi: 10.1186/s12906-018-2233-6.
5
Protein phosphatase 1 activation and alternative splicing of Bcl-X and Mcl-1 by EGCG + ibuprofen.表没食子儿茶素没食子酸酯（EGCG）与布洛芬共同作用下蛋白磷酸酶1的激活以及Bcl-X和Mcl-1的可变剪接
J Cell Biochem. 2008 Jul 1;104(4):1491-9. doi: 10.1002/jcb.21725.
6
Emetine regulates the alternative splicing of caspase 9 in tumor cells.依米丁调节肿瘤细胞中半胱天冬酶9的可变剪接。
Oncol Lett. 2011 Nov;2(6):1309-1312. doi: 10.3892/ol.2011.395. Epub 2011 Aug 29.
7
NHE3 function and phosphorylation are regulated by a calyculin A-sensitive phosphatase.NHE3 的功能和磷酸化受钙调神经磷酸酶敏感的磷酸酶调节。
Am J Physiol Renal Physiol. 2010 Mar;298(3):F745-53. doi: 10.1152/ajprenal.00182.2009. Epub 2009 Dec 16.
8
Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis.BC200对Bcl-x可变剪接的调控有助于乳腺癌的发病机制。
Cell Death Dis. 2016 Jun 9;7(6):e2262. doi: 10.1038/cddis.2016.168.
9
PP1/PP2A phosphatase inhibition-induced metaplasticity in protein synthesis blocker-treated hippocampal slices: LTP and LTD, or There and Back again.蛋白合成抑制剂处理的海马切片中 PP1/PP2A 磷酸酶抑制诱导的代谢可塑性：LTP 和 LTD，或有去有回。
Biochem Biophys Res Commun. 2021 Jun 18;558:64-70. doi: 10.1016/j.bbrc.2021.04.061. Epub 2021 Apr 23.
10
A G-tract element in apoptotic agents-induced alternative splicing.凋亡因子诱导的可变剪接中的G-序列元件
Nucleic Acids Res. 2008 Jun;36(10):3320-31. doi: 10.1093/nar/gkn207. Epub 2008 Apr 24.
引用本文的文献
1
Emetine dihydrochloride alleviated radiation-induced lung injury through inhibiting EMT.盐酸埃替啡啶通过抑制 EMT 缓解放射性肺损伤。
J Cell Mol Med. 2023 Dec;27(23):3839-3850. doi: 10.1111/jcmm.17959. Epub 2023 Sep 18.
2
Application of emetine in SARS-CoV-2 treatment: regulation of p38 MAPK signaling pathway for preventing emetine-induced cardiac complications.盐酸依米丁在 SARS-CoV-2 治疗中的应用：调控 p38MAPK 信号通路预防盐酸依米丁诱导的心脏并发症。
Cell Cycle. 2022 Nov;21(22):2379-2386. doi: 10.1080/15384101.2022.2100575. Epub 2022 Jul 19.
3
A High-Content Screen for C/EBPα Expression Identifies Novel Therapeutic Agents in Dedifferentiated Liposarcoma.一种高内涵筛选方法用于检测 C/EBPα 的表达，从而鉴定去分化脂肪肉瘤的新型治疗药物。
Clin Cancer Res. 2022 Jan 1;28(1):175-186. doi: 10.1158/1078-0432.CCR-19-2486. Epub 2021 Oct 19.
4
System level characterization of small molecule drugs and their affected long noncoding RNAs.小分子药物及其影响的长链非编码RNA的系统水平表征
Aging (Albany NY). 2019 Dec 18;11(24):12428-12451. doi: 10.18632/aging.102581.
5
Oxidative stress as candidate therapeutic target to overcome microenvironmental protection of CLL.氧化应激作为克服 CLL 微环境保护的候选治疗靶点。
Leukemia. 2020 Jan;34(1):115-127. doi: 10.1038/s41375-019-0513-x. Epub 2019 Jul 12.
6
Alternative splicing in human cancer cells is modulated by the amiloride derivative 3,5-diamino-6-chloro-N-(N-(2,6-dichlorobenzoyl)carbamimidoyl)pyrazine-2-carboxide.人类癌细胞中的可变剪接受阿米洛利衍生物 3,5-二氨基-6-氯-N-(N-(2,6-二氯苯甲酰)氨甲酰基)吡嗪-2-甲酰胺的调节。
Mol Oncol. 2019 Aug;13(8):1744-1762. doi: 10.1002/1878-0261.12524. Epub 2019 Jun 1.
7
BCL-2 family isoforms in apoptosis and cancer.BCL-2 家族在细胞凋亡和癌症中的亚型。
Cell Death Dis. 2019 Feb 21;10(3):177. doi: 10.1038/s41419-019-1407-6.
8
A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes.高通量筛选通过靶向 RNA G-四联体识别剪接的小分子调节剂。
Nucleic Acids Res. 2019 Apr 23;47(7):3667-3679. doi: 10.1093/nar/gkz036.
9
Retrograde axonal transport of rabies virus is unaffected by interferon treatment but blocked by emetine locally in axons.狂犬病病毒的逆行轴突转运不受干扰素治疗的影响，但在轴突中被依米丁局部阻断。
PLoS Pathog. 2018 Jul 20;14(7):e1007188. doi: 10.1371/journal.ppat.1007188. eCollection 2018 Jul.
10
Homoharringtonine regulates the alternative splicing of Bcl-x and caspase 9 through a protein phosphatase 1-dependent mechanism.高三尖杉酯碱通过蛋白磷酸酶 1 依赖的机制调节 Bcl-x 和 caspase 9 的选择性剪接。
BMC Complement Altern Med. 2018 May 22;18(1):164. doi: 10.1186/s12906-018-2233-6.
本文引用的文献
1
siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma cells to chemotherapeutic drugs.小干扰RNA介导的Bcl-2和Bcl-xl基因沉默使人类肝母细胞瘤细胞对化疗药物敏感。
Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):450-6. doi: 10.1111/j.1440-1681.2007.04593.x.
2
Down-regulation of Bcl-XL by RNA interference suppresses cell growth and induces apoptosis in human esophageal cancer cells.通过RNA干扰下调Bcl-XL可抑制人食管癌细胞的生长并诱导其凋亡。
World J Gastroenterol. 2006 Dec 14;12(46):7472-7. doi: 10.3748/wjg.v12.i46.7472.
3
Bcl-XL small interfering RNA enhances sensitivity of Hepg2 hepatocellular carcinoma cells to 5-fluorouracil and hydroxycamptothecin.Bcl-XL小干扰RNA增强Hepg2肝癌细胞对5-氟尿嘧啶和羟基喜树碱的敏感性。
Acta Biochim Biophys Sin (Shanghai). 2006 Oct;38(10):704-10. doi: 10.1111/j.1745-7270.2006.00212.x.
4
Bcl-xL is overexpressed in hormone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak.Bcl-xL在激素抵抗性前列腺癌中过表达，并通过与促凋亡蛋白Bak相互作用促进LNCaP细胞存活。
Endocrinology. 2006 Oct;147(10):4960-7. doi: 10.1210/en.2006-0502. Epub 2006 Jun 22.
5
Structural basis for inhibition of protein synthesis by emetine and cycloheximide based on an analogy between ipecac alkaloids and glutarimide antibiotics.基于吐根生物碱与戊二酰亚胺类抗生素之间的类比，阐明吐根碱和放线菌酮抑制蛋白质合成的结构基础。
Proc Natl Acad Sci U S A. 1966 Dec;56(6):1867-74. doi: 10.1073/pnas.56.6.1867.
6
Regulation of apoptosis by alternative pre-mRNA splicing.可变前体信使核糖核酸剪接对细胞凋亡的调控
Mol Cell. 2005 Jul 1;19(1):1-13. doi: 10.1016/j.molcel.2005.05.026.
7
Bcl-XL small interfering RNA suppresses the proliferation of 5-fluorouracil-resistant human colon cancer cells.Bcl-XL小干扰RNA抑制5-氟尿嘧啶耐药人结肠癌细胞的增殖。
Mol Cancer Ther. 2005 Mar;4(3):451-6. doi: 10.1158/1535-7163.MCT-04-0162.
8
Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease.Bcl-xL在卵巢癌中的表达与化疗耐药及疾病复发相关。
Gynecol Oncol. 2005 Feb;96(2):287-95. doi: 10.1016/j.ygyno.2004.10.026.
9
Regulation of alternative splicing of Bcl-x by IL-6, GM-CSF and TPA.白细胞介素-6、粒细胞巨噬细胞集落刺激因子和佛波酯对Bcl-x可变剪接的调控
Cell Res. 2004 Dec;14(6):473-9. doi: 10.1038/sj.cr.7290250.
10
Bcl-x(L) antisense oligonucleotides radiosensitise colon cancer cells.Bcl-x（L）反义寡核苷酸使结肠癌细胞对放疗敏感。
Br J Cancer. 2003 Oct 6;89(7):1352-7. doi: 10.1038/sj.bjc.6601254.
Zotero 插件