• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

与 Tak1 结合的无活性 Tlk 增加 p38 MAPK 活性，从而延长 G2 期。

Inactive Tlk associating with Tak1 increases p38 MAPK activity to prolong the G2 phase.

机构信息

Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, 112-22, Taiwan, Republic of China.

Center for Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, 115-61, Taiwan, Republic of China.

出版信息

Sci Rep. 2019 Feb 13;9(1):1885. doi: 10.1038/s41598-018-36137-1.

DOI:10.1038/s41598-018-36137-1
PMID:30760733
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6374402/
Abstract

To guard genome integrity, response mechanisms coordinately execute the G2/M checkpoint in responding to stress. p38 MAPK is activated to prolong the G2 phase for completion of damage repair. Tlk activity is required for DNA repair, chromosome segregation and G2 recovery. However, the involvement of Tlk in G2 recovery differs from previous findings that Tlk overexpression delays the G2/M transition. To clarify this difference, genetic interaction experiments were performed using the second mitotic wave as model system. The results indicate that Tlk overexpression prolongs the G2 phase through p38 MAPK activation, independent of Tlk kinase activity. The results of co-immunoprecipitation, database search and RNAi screening suggest that eEF1α1 and Hsc70-5 links Tlk to Tak1. Reduced gene activities of Tlk, Hsc70-5, eEF1α1 and/or Tak1 couldn't prolong the G2 phase induced by heat shock, indicating that these proteins work together to elevate p38 MAPK activity. In contrast, a high level of wild type Tlk decreases phosphorylated p38 MAPK levels. Thus, the difference is explained by a dual function of Tlk. When under stress, inactive Tlk increases p38 MAPK activity to prolong the G2 phase, and then activated Tlk modulates activities of p38 MAPK and Asf1 to promote G2 recovery afterwards.

摘要

为了保护基因组的完整性，响应机制通过协调执行 G2/M 检查点来应对压力。p38 MAPK 被激活以延长 G2 期，以完成损伤修复。Tlk 活性对于 DNA 修复、染色体分离和 G2 恢复是必需的。然而，Tlk 在 G2 恢复中的参与与之前的发现不同，即 Tlk 过表达会延迟 G2/M 转换。为了澄清这种差异，使用第二次有丝分裂波作为模型系统进行了遗传相互作用实验。结果表明，Tlk 过表达通过激活 p38 MAPK 延长 G2 期，而与 Tlk 激酶活性无关。共免疫沉淀、数据库搜索和 RNAi 筛选的结果表明，eEF1α1 和 Hsc70-5 将 Tlk 与 Tak1 联系起来。Tlk、Hsc70-5、eEF1α1 和/或 Tak1 的基因活性降低不能延长热休克诱导的 G2 期，表明这些蛋白共同作用以提高 p38 MAPK 活性。相比之下，高水平的野生型 Tlk 降低了磷酸化 p38 MAPK 的水平。因此，差异可以通过 Tlk 的双重功能来解释。在受到压力时，非活性 Tlk 增加 p38 MAPK 活性以延长 G2 期，然后激活的 Tlk 调节 p38 MAPK 和 Asf1 的活性以促进随后的 G2 恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/a1763209fc2f/41598_2018_36137_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/4ee28591b3c1/41598_2018_36137_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/e7b9c0bdb71e/41598_2018_36137_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/4f738b697888/41598_2018_36137_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/603eb12aaa48/41598_2018_36137_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/ff206607b591/41598_2018_36137_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/33e526b9464f/41598_2018_36137_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/a1763209fc2f/41598_2018_36137_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/4ee28591b3c1/41598_2018_36137_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/e7b9c0bdb71e/41598_2018_36137_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/4f738b697888/41598_2018_36137_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/603eb12aaa48/41598_2018_36137_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/ff206607b591/41598_2018_36137_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/33e526b9464f/41598_2018_36137_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc4c/6374402/a1763209fc2f/41598_2018_36137_Fig7_HTML.jpg

相似文献

1
Inactive Tlk associating with Tak1 increases p38 MAPK activity to prolong the G2 phase.与 Tak1 结合的无活性 Tlk 增加 p38 MAPK 活性，从而延长 G2 期。
Sci Rep. 2019 Feb 13;9(1):1885. doi: 10.1038/s41598-018-36137-1.
2
Phosphorylation of heat shock protein 27 antagonizes TNF-α induced HeLa cell apoptosis via regulating TAK1 ubiquitination and activation of p38 and ERK signaling.热休克蛋白 27 的磷酸化通过调节 TAK1 泛素化和激活 p38 和 ERK 信号通路拮抗 TNF-α 诱导的 HeLa 细胞凋亡。
Cell Signal. 2014 Jul;26(7):1616-25. doi: 10.1016/j.cellsig.2014.03.015. Epub 2014 Mar 29.
3
The p53 pathway is synergized by p38 MAPK signaling to mediate 11,11'-dideoxyverticillin-induced G2/M arrest.p53信号通路通过p38丝裂原活化蛋白激酶（MAPK）信号传导协同作用，介导11,11'-二脱氧弗替西林诱导的G2/M期阻滞。
FEBS Lett. 2005 Jul 4;579(17):3683-90. doi: 10.1016/j.febslet.2005.05.053.
4
UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway.紫外线诱导的 G2 检验点依赖于 p38MAPK 和 ATR-Chk1 通路的最小激活。
J Cell Sci. 2013 May 1;126(Pt 9):1923-30. doi: 10.1242/jcs.118265. Epub 2013 Feb 27.
5
The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1.TGFβ 诱导的 p38 丝裂原活化蛋白激酶的磷酸化和激活是由 MAP3K4 和 MAP3K10 介导的，但不是 TAK1。
Open Biol. 2013 Jun 12;3(6):130067. doi: 10.1098/rsob.130067.
6
TAO kinases mediate activation of p38 in response to DNA damage.TAO激酶介导p38在DNA损伤应答中的激活。
EMBO J. 2007 Apr 18;26(8):2005-14. doi: 10.1038/sj.emboj.7601668. Epub 2007 Mar 29.
7
TGF-beta-activated kinase 1 and TAK1-binding protein 1 cooperate to mediate TGF-beta1-induced MKK3-p38 MAPK activation and stimulation of type I collagen.转化生长因子β激活激酶1与TAK1结合蛋白1协同介导转化生长因子β1诱导的MKK3-p38丝裂原活化蛋白激酶激活及I型胶原蛋白的刺激。
Am J Physiol Renal Physiol. 2007 May;292(5):F1471-8. doi: 10.1152/ajprenal.00485.2006. Epub 2007 Feb 13.
8
HGFK1 inhibits bone metastasis in breast cancer through the TAK1/p38 MAPK signaling pathway.HGFK1 通过 TAK1/p38 MAPK 信号通路抑制乳腺癌骨转移。
Cancer Gene Ther. 2012 Sep;19(9):601-8. doi: 10.1038/cgt.2012.38. Epub 2012 Jul 6.
9
Developmental regulation of mitogen-activated protein kinase-activated kinases-2 and -3 (MAPKAPK-2/-3) in vivo during corpus luteum formation in the rat.大鼠黄体形成过程中丝裂原活化蛋白激酶激活的激酶-2和-3（MAPKAPK-2/-3）在体内的发育调控。
Mol Endocrinol. 2001 May;15(5):716-33. doi: 10.1210/mend.15.5.0634.
10
TGF-beta-activating kinase-1 inhibits cell cycle and expression of cyclin D1 and A in LLC-PK1 cells.转化生长因子-β激活激酶1抑制LLC-PK1细胞的细胞周期以及细胞周期蛋白D1和A的表达。
Kidney Int. 1999 Oct;56(4):1378-90. doi: 10.1046/j.1523-1755.1999.00665.x.

引用本文的文献

1
TAK1 inhibition increases proliferation and differentiation of chick retinal cells.TAK1抑制作用可增强鸡视网膜细胞的增殖和分化。
Front Cell Dev Biol. 2022 Sep 13;10:698233. doi: 10.3389/fcell.2022.698233. eCollection 2022.
2
The Tousled-like kinases regulate genome and epigenome stability: implications in development and disease.Tousled 样激酶调节基因组和表观基因组稳定性：在发育和疾病中的意义。
Cell Mol Life Sci. 2019 Oct;76(19):3827-3841. doi: 10.1007/s00018-019-03208-z. Epub 2019 Jul 13.

本文引用的文献

1
Molecular basis of Tousled-Like Kinase 2 activation.Tousled 样激酶 2 的激活的分子基础。
Nat Commun. 2018 Jun 28;9(1):2535. doi: 10.1038/s41467-018-04941-y.
2
p38 MAPK inhibits autophagy and promotes microglial inflammatory responses by phosphorylating ULK1.p38 MAPK 通过磷酸化 ULK1 抑制自噬并促进小胶质细胞炎症反应。
J Cell Biol. 2018 Jan 2;217(1):315-328. doi: 10.1083/jcb.201701049. Epub 2017 Dec 1.
3
GRP78 at the Centre of the Stage in Cancer and Neuroprotection.GRP78在癌症与神经保护中处于核心地位。
Front Neurosci. 2017 Apr 5;11:177. doi: 10.3389/fnins.2017.00177. eCollection 2017.
4
Pits, a protein interacting with Ttk69 and Sin3A, has links to histone deacetylation.陷窝蛋白与 Ttk69 和 Sin3A 相互作用，与组蛋白去乙酰化有关。
Sci Rep. 2016 Sep 13;6:33388. doi: 10.1038/srep33388.
5
Amplification of TLK2 Induces Genomic Instability via Impairing the G2-M Checkpoint.TLK2的扩增通过损害G2-M检查点诱导基因组不稳定。
Mol Cancer Res. 2016 Oct;14(10):920-927. doi: 10.1158/1541-7786.MCR-16-0161. Epub 2016 Aug 3.
6
Tousled-like kinase 2 regulates recovery from a DNA damage-induced G2 arrest.类蓬松激酶2调节DNA损伤诱导的G2期阻滞后的恢复。
EMBO Rep. 2016 May;17(5):659-70. doi: 10.15252/embr.201540767. Epub 2016 Mar 1.
7
Tousled-like kinase mediated a new type of cell death pathway in Drosophila.类蓬松激酶介导了果蝇中一种新型的细胞死亡途径。
Cell Death Differ. 2016 Jan;23(1):146-57. doi: 10.1038/cdd.2015.77. Epub 2015 Jun 19.
8
Modulation of cell morphogenesis by tousled-like kinase in the Drosophila follicle cell.果蝇卵泡细胞中凌乱样激酶对细胞形态发生的调控
Dev Dyn. 2015 Jul;244(7):852-65. doi: 10.1002/dvdy.24292. Epub 2015 Jun 22.
9
The Catalytic Subunit of DNA-Dependent Protein Kinase Coordinates with Polo-Like Kinase 1 to Facilitate Mitotic Entry.DNA依赖蛋白激酶的催化亚基与Polo样激酶1协同作用以促进有丝分裂进入。
Neoplasia. 2015 Apr;17(4):329-38. doi: 10.1016/j.neo.2015.02.004.
10
A kinase-independent role for EGF receptor in autophagy initiation.表皮生长因子受体在自噬起始中不依赖激酶的作用。
Cell. 2015 Jan 15;160(1-2):145-60. doi: 10.1016/j.cell.2014.12.006.