为精确适配磷脂酰肌醇3-激酶相关激酶而分支Tel2途径。
Branching the Tel2 pathway for exact fit on phosphatidylinositol 3-kinase-related kinases.
作者信息
Sugimoto Katsunori
机构信息
Department of Microbiology, Biochemistry and Molecular Genetics, International Center for Public Health, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, 07103, USA.
出版信息
Curr Genet. 2018 Oct;64(5):965-970. doi: 10.1007/s00294-018-0817-9. Epub 2018 Feb 22.
Abstract
Phosphatidylinositol 3-kinase-related kinases (PIKKs), are structurally related to phosphatidylinositol 3-kinase (lipid kinase), but possess protein kinase activities. PIKKs include ATM, ATR, DNA-PK, mTOR and SMG1, key regulators of cell proliferation and genome maintenance. TRRAP, which is devoid of protein kinase activity, is the sixth member of the PIKK family. PIKK family members are gigantic proteins in the range of 300-500 kDa. It has become apparent in the last decade that the stability or maturation of the PIKK family members depends on a molecular chaperone called the Tel2-Tti1-Tti2 (TTT) complex. Several lines of evidence have established a model in which TTT connects to the Hsp90 chaperone through the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex in mammalian and yeast cells. However, recent studies of yeast cells indicate that TTT is able to form different complexes. These observations raise a possibility that several different mechanisms regulate TTT-mediated protein stability of PIKKs.
摘要
磷脂酰肌醇3-激酶相关激酶（PIKKs）在结构上与磷脂酰肌醇3-激酶（脂质激酶）相关，但具有蛋白激酶活性。PIKKs包括ATM、ATR、DNA-PK、mTOR和SMG1，它们是细胞增殖和基因组维持的关键调节因子。缺乏蛋白激酶活性的TRRAP是PIKK家族的第六个成员。PIKK家族成员是分子量在300 - 500 kDa范围内的巨大蛋白质。在过去十年中已经很明显，PIKK家族成员的稳定性或成熟取决于一种称为Tel2-Tti1-Tti2（TTT）复合物的分子伴侣。多项证据建立了一个模型，在哺乳动物和酵母细胞中，TTT通过Rvb1-Rvb2-Tah1-Pih1（R2TP）复合物与Hsp90伴侣蛋白相连。然而，最近对酵母细胞的研究表明，TTT能够形成不同的复合物。这些观察结果提出了一种可能性，即几种不同的机制调节TTT介导的PIKKs蛋白稳定性。
相似文献
1
Branching the Tel2 pathway for exact fit on phosphatidylinositol 3-kinase-related kinases.为精确适配磷脂酰肌醇3-激酶相关激酶而分支Tel2途径。
Curr Genet. 2018 Oct;64(5):965-970. doi: 10.1007/s00294-018-0817-9. Epub 2018 Feb 22.
2
TTT (Tel2-Tti1-Tti2) Complex, the Co-Chaperone of PIKKs and a Potential Target for Cancer Chemotherapy.TTT（Tel2-Tti1-Tti2）复合物，PIKKs 的共伴侣，癌症化疗的潜在靶点。
Int J Mol Sci. 2023 May 5;24(9):8268. doi: 10.3390/ijms24098268.
3
Two separate pathways regulate protein stability of ATM/ATR-related protein kinases Mec1 and Tel1 in budding yeast.在芽殖酵母中，两条独立的途径调节ATM/ATR相关蛋白激酶Mec1和Tel1的蛋白质稳定性。
PLoS Genet. 2017 Aug 21;13(8):e1006873. doi: 10.1371/journal.pgen.1006873. eCollection 2017 Aug.
4
CK2 phospho-independent assembly of the Tel2-associated stress-signaling complexes in Schizosaccharomyces pombe.粟酒裂殖酵母中与Tel2相关的应激信号复合物的CK2非磷酸化依赖性组装。
Genes Cells. 2017 Jan;22(1):59-70. doi: 10.1111/gtc.12454. Epub 2016 Dec 9.
5
Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.Tel2 结构和功能在 mTOR 和 ATR 复合物的 HSP90 依赖性成熟中的作用。
Genes Dev. 2010 Sep 15;24(18):2019-30. doi: 10.1101/gad.1956410. Epub 2010 Aug 27.
6
Saccharomyces cerevisiae Tti2 Regulates PIKK Proteins and Stress Response.酿酒酵母Tti2调节PIKK蛋白和应激反应。
G3 (Bethesda). 2016 Jun 1;6(6):1649-59. doi: 10.1534/g3.116.029520.
7
CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.CK2 磷酸化依赖性 R2TP 复合物与 TEL2 的结合对于 mTOR 和 SMG1 的稳定性至关重要。
Mol Cell. 2010 Sep 24;39(6):839-50. doi: 10.1016/j.molcel.2010.08.037.
8
Structural basis for phosphorylation-dependent recruitment of Tel2 to Hsp90 by Pih1.Pih1介导磷酸化依赖性的Tel2募集至Hsp90的结构基础。
Structure. 2014 Jun 10;22(6):805-18. doi: 10.1016/j.str.2014.04.001. Epub 2014 May 1.
9
Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone.TELO2-TTI1-TTI2 复合物的结构及其在 TOR 招募到 R2TP 伴侣蛋白中的功能。
Cell Rep. 2021 Jul 6;36(1):109317. doi: 10.1016/j.celrep.2021.109317.
10
Structure of the Human TELO2-TTI1-TTI2 Complex.人类 TELO2-TTI1-TTI2 复合物的结构。
J Mol Biol. 2022 Jan 30;434(2):167370. doi: 10.1016/j.jmb.2021.167370. Epub 2021 Nov 24.
引用本文的文献
1
Design, Synthesis, and Biological Evaluation of Potent and Selective Inhibitors of Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase for the Efficient Treatment of Cancer.设计、合成及对ATR 激酶的高效治疗癌症的强效和选择性抑制剂的生物学评估
Molecules. 2023 Jun 2;28(11):4521. doi: 10.3390/molecules28114521.
2
TTT (Tel2-Tti1-Tti2) Complex, the Co-Chaperone of PIKKs and a Potential Target for Cancer Chemotherapy.TTT（Tel2-Tti1-Tti2）复合物，PIKKs 的共伴侣，癌症化疗的潜在靶点。
Int J Mol Sci. 2023 May 5;24(9):8268. doi: 10.3390/ijms24098268.
3
Genome-wide association analysis for drought tolerance and associated traits in faba bean ( L.).蚕豆（Vicia faba L.）耐旱性及相关性状的全基因组关联分析
Front Plant Sci. 2023 Feb 1;14:1091875. doi: 10.3389/fpls.2023.1091875. eCollection 2023.
4
Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.双等位基因 TTI1 变异导致常染色体隐性遗传性神经发育障碍伴小头畸形。
Am J Hum Genet. 2023 Mar 2;110(3):499-515. doi: 10.1016/j.ajhg.2023.01.006. Epub 2023 Jan 31.
5
Multi-Level Control of the ATM/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer.三阴性乳腺癌中转录因子 E4F1 对 ATM/ATR-CHK1 轴的多级调控
Int J Mol Sci. 2022 Aug 16;23(16):9217. doi: 10.3390/ijms23169217.
6
Novel Homozygous TTI2 Variant Causing Autosomal Recessive Syndromic Intellectual Disability and Primary Microcephaly from Pakistan: A Case Report (Exome Report).来自巴基斯坦的导致常染色体隐性综合征性智力残疾和原发性小头畸形的新型纯合子TTI2变异：一例报告（外显子组报告）
Case Rep Genet. 2022 Aug 12;2022:2766957. doi: 10.1155/2022/2766957. eCollection 2022.
7
Systems genetics in the rat HXB/BXH family identifies Tti2 as a pleiotropic quantitative trait gene for adult hippocampal neurogenesis and serum glucose.大鼠 HXB/BXH 家系中的系统遗传学研究将 Tti2 鉴定为成年海马神经发生和血清葡萄糖的多效性数量性状基因。
PLoS Genet. 2022 Apr 4;18(4):e1009638. doi: 10.1371/journal.pgen.1009638. eCollection 2022 Apr.
8
Functional analysis of a novel de novo variant in PPP5C associated with microcephaly, seizures, and developmental delay.一种与小头畸形、癫痫和发育迟缓相关的 PPP5C 新型从头变异的功能分析。
Mol Genet Metab. 2022 May;136(1):65-73. doi: 10.1016/j.ymgme.2022.03.007. Epub 2022 Mar 22.
9
The interaction between RPAP3 and TRBP reveals a possible involvement of the HSP90/R2TP chaperone complex in the regulation of miRNA activity.RPAP3 与 TRBP 的相互作用揭示了 HSP90/R2TP 伴侣复合物可能参与 miRNA 活性的调节。
Nucleic Acids Res. 2022 Feb 28;50(4):2172-2189. doi: 10.1093/nar/gkac086.
10
DNA repair, recombination, and damage signaling.DNA 修复、重组和损伤信号转导。
Genetics. 2022 Feb 4;220(2). doi: 10.1093/genetics/iyab178.
本文引用的文献
1
Two separate pathways regulate protein stability of ATM/ATR-related protein kinases Mec1 and Tel1 in budding yeast.在芽殖酵母中，两条独立的途径调节ATM/ATR相关蛋白激酶Mec1和Tel1的蛋白质稳定性。
PLoS Genet. 2017 Aug 21;13(8):e1006873. doi: 10.1371/journal.pgen.1006873. eCollection 2017 Aug.
2
How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches.热休克蛋白90（Hsp90）和细胞分裂周期蛋白37（Cdc37）如何调控激酶分子开关。
Trends Biochem Sci. 2017 Oct;42(10):799-811. doi: 10.1016/j.tibs.2017.07.002. Epub 2017 Aug 4.
3
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.ATM、ATR 和 DNA-PK：DNA 损伤反应中的三位一体。
Mol Cell. 2017 Jun 15;66(6):801-817. doi: 10.1016/j.molcel.2017.05.015.
4
Regulation of Rvb1/Rvb2 by a Domain within the INO80 Chromatin Remodeling Complex Implicates the Yeast Rvbs as Protein Assembly Chaperones.INO80染色质重塑复合物内的一个结构域对Rvb1/Rvb2的调控表明酵母Rvbs作为蛋白质组装伴侣。
Cell Rep. 2017 Jun 6;19(10):2033-2044. doi: 10.1016/j.celrep.2017.05.029.
5
The HSP90 chaperone machinery.HSP90 伴侣分子机器。
Nat Rev Mol Cell Biol. 2017 Jun;18(6):345-360. doi: 10.1038/nrm.2017.20. Epub 2017 Apr 21.
6
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair.DNA-PKcs 结构提示了一种变构机制，可调节 DNA 双链断裂修复。
Science. 2017 Feb 3;355(6324):520-524. doi: 10.1126/science.aak9654. Epub 2017 Feb 2.
7
CK2 phospho-independent assembly of the Tel2-associated stress-signaling complexes in Schizosaccharomyces pombe.粟酒裂殖酵母中与Tel2相关的应激信号复合物的CK2非磷酸化依赖性组装。
Genes Cells. 2017 Jan;22(1):59-70. doi: 10.1111/gtc.12454. Epub 2016 Dec 9.
8
Regulation of non-homologous end joining via post-translational modifications of components of the ligation step.通过连接步骤各组分的翻译后修饰对非同源末端连接进行调控。
Curr Genet. 2017 Aug;63(4):591-605. doi: 10.1007/s00294-016-0670-7. Epub 2016 Dec 3.
9
Hsp90 mediates the crosstalk between galactose metabolism and cell morphology pathways in yeast.热休克蛋白90（Hsp90）介导酵母中半乳糖代谢与细胞形态通路之间的相互作用。
Curr Genet. 2017 Feb;63(1):23-27. doi: 10.1007/s00294-016-0614-2. Epub 2016 May 21.
10
Nonsense-Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part of the Story.无义介导的mRNA衰变：缺陷转录本的降解只是其中一部分。
Annu Rev Genet. 2015;49:339-66. doi: 10.1146/annurev-genet-112414-054639. Epub 2015 Oct 2.
Zotero 插件