CKIP-1 将 Smurf1 泛素连接酶与蛋白酶体的 Rpt6 亚基偶联，以促进底物降解。
CKIP-1 couples Smurf1 ubiquitin ligase with Rpt6 subunit of proteasome to promote substrate degradation.
机构信息
State Key Laboratory of Proteomics, Department of Genomics and Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
出版信息
EMBO Rep. 2012 Nov 6;13(11):1004-11. doi: 10.1038/embor.2012.144. Epub 2012 Oct 2.
Abstract
CKIP-1 is an activator of the Smurf1 ubiquitin ligase acting to promote the ubiquitylation of Smad5 and MEKK2. The mechanisms involved in the recognition and degradation of these substrates by the proteasome remain unclear. Here, we show that CKIP-1, through its leucine zipper, interacts directly with the Rpt6 ATPase of the 19S regulatory particle of the proteasome. CKIP-1 mediates the Smurf1-Rpt6 interaction and delivers the ubiquitylated substrates to the proteasome. Depletion of CKIP-1 reduces the degradation of Smurf1 and its substrates by Rpt6. These findings reveal an unexpected adaptor role of CKIP-1 in coupling the ubiquitin ligase and the proteasome.
摘要
CKIP-1 是 Smurf1 泛素连接酶的激活剂，可促进 Smad5 和 MEKK2 的泛素化。蛋白酶体识别和降解这些底物的机制仍不清楚。在这里，我们发现 CKIP-1 通过其亮氨酸拉链与蛋白酶体 19S 调节颗粒的 Rpt6 ATP 酶直接相互作用。CKIP-1 介导 Smurf1-Rpt6 相互作用，并将泛素化的底物递送到蛋白酶体。CKIP-1 的耗竭减少了 Rpt6 对 Smurf1 及其底物的降解。这些发现揭示了 CKIP-1 在连接泛素连接酶和蛋白酶体中的一个意外衔接作用。
相似文献
1
CKIP-1 couples Smurf1 ubiquitin ligase with Rpt6 subunit of proteasome to promote substrate degradation.CKIP-1 将 Smurf1 泛素连接酶与蛋白酶体的 Rpt6 亚基偶联，以促进底物降解。
EMBO Rep. 2012 Nov 6;13(11):1004-11. doi: 10.1038/embor.2012.144. Epub 2012 Oct 2.
2
The Xanthomonas campestris type III effector XopJ proteolytically degrades proteasome subunit RPT6.野油菜黄单胞菌III型效应蛋白XopJ可通过蛋白水解作用降解蛋白酶体亚基RPT6。
Plant Physiol. 2015 May;168(1):107-19. doi: 10.1104/pp.15.00132. Epub 2015 Mar 4.
3
PDLIM7 Synergizes With PDLIM2 and p62/Sqstm1 to Inhibit Inflammatory Signaling by Promoting Degradation of the p65 Subunit of NF-κB.PDLIM7 与 PDLIM2 和 p62/Sqstm1 协同作用，通过促进 NF-κB p65 亚基的降解来抑制炎症信号。
Front Immunol. 2020 Aug 4;11:1559. doi: 10.3389/fimmu.2020.01559. eCollection 2020.
4
Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation.去泛素化酶 FAM/USP9X 与 E3 泛素连接酶 SMURF1 蛋白相互作用，并保护其免受连接酶活性依赖性的自身降解。
J Biol Chem. 2013 Feb 1;288(5):2976-85. doi: 10.1074/jbc.M112.430066. Epub 2012 Nov 26.
5
Valosin-containing Protein (VCP)/p97 Segregase Mediates Proteolytic Processing of Cockayne Syndrome Group B (CSB) in Damaged Chromatin.含缬酪肽蛋白（VCP）/p97解聚酶介导受损染色质中柯凯恩综合征B组（CSB）的蛋白水解加工。
J Biol Chem. 2016 Apr 1;291(14):7396-408. doi: 10.1074/jbc.M115.705350. Epub 2016 Jan 29.
6
Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1.通过CKIP-1激活靶向HECT型泛素连接酶Smurf1的WW结构域连接区。
Nat Cell Biol. 2008 Aug;10(8):994-1002. doi: 10.1038/ncb1760. Epub 2008 Jul 20.
7
REGgamma proteasome mediates degradation of the ubiquitin ligase Smurf1.REGgamma 蛋白酶体介导泛素连接酶 Smurf1 的降解。
FEBS Lett. 2010 Jul 16;584(14):3021-7. doi: 10.1016/j.febslet.2010.05.034. Epub 2010 May 24.
8
Identification of a quality-control factor that monitors failures during proteasome assembly.鉴定一种质量控制因子，该因子可监测蛋白酶体组装过程中的故障。
Science. 2021 Aug 27;373(6558):998-1004. doi: 10.1126/science.abc6500.
9
CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys.CKIP-1 通过介导 Smurf1 影响 Nrf2 和 Keap1 的多泛素化来抵抗 HG 诱导的 GMCs 和糖尿病小鼠肾脏纤维化。
Free Radic Biol Med. 2018 Feb 1;115:338-350. doi: 10.1016/j.freeradbiomed.2017.12.013. Epub 2017 Dec 14.
10
HSP70 mediates degradation of the p65 subunit of nuclear factor κB to inhibit inflammatory signaling.热休克蛋白70（HSP70）介导核因子κB的p65亚基降解，以抑制炎症信号传导。
Sci Signal. 2014 Dec 16;7(356):ra119. doi: 10.1126/scisignal.2005533.
引用本文的文献
1
The Discovery of a Specific CKIP-1 Ligand for the Potential Treatment of Disuse Osteoporosis.发现一种特定的 CKIP-1 配体，有望用于治疗废用性骨质疏松症。
Int J Mol Sci. 2024 Aug 15;25(16):8870. doi: 10.3390/ijms25168870.
2
Substrate-specific effects of natural genetic variation on proteasome activity.天然遗传变异对蛋白酶体活性的底物特异性影响。
PLoS Genet. 2023 May 1;19(5):e1010734. doi: 10.1371/journal.pgen.1010734. eCollection 2023 May.
3
PLEKHO1 knockdown inhibits RCC cell viability in vitro and in vivo, potentially by the Hippo and MAPK/JNK pathways.PLEKHO1 敲低抑制 RCC 细胞在体外和体内的活力，可能通过 Hippo 和 MAPK/JNK 通路。
Int J Oncol. 2019 Jul;55(1):81-92. doi: 10.3892/ijo.2019.4819. Epub 2019 May 30.
4
Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis.成骨细胞 PLEKHO1 促进类风湿关节炎的关节炎症。
EBioMedicine. 2019 Mar;41:538-555. doi: 10.1016/j.ebiom.2019.02.009. Epub 2019 Feb 26.
5
The role of CKIP-1 in osteoporosis development and treatment.CKIP-1在骨质疏松症发生发展及治疗中的作用。
Bone Joint Res. 2018 Apr 12;7(2):173-178. doi: 10.1302/2046-3758.72.BJR-2017-0172.R1. eCollection 2018 Feb.
6
Proteasomal degradation of γ-aminobutyric acidB receptors is mediated by the interaction of the GABAB2 C terminus with the proteasomal ATPase Rtp6 and regulated by neuronal activity.γ-氨基丁酸 B 受体的蛋白酶体降解是由 GABAB2 C 末端与蛋白酶体 ATP 酶 Rtp6 的相互作用介导的，并受神经元活动的调节。
J Biol Chem. 2014 Mar 14;289(11):7738-46. doi: 10.1074/jbc.M113.541987. Epub 2014 Jan 30.
7
CKIP-1 is an intrinsic negative regulator of T-cell activation through an interaction with CARMA1.CKIP-1是一种通过与CARMA1相互作用来对T细胞激活起内在负调控作用的分子。
PLoS One. 2014 Jan 17;9(1):e85762. doi: 10.1371/journal.pone.0085762. eCollection 2014.
本文引用的文献
1
A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy.一种针对骨形成表面的递药系统，以促进基于 RNAi 的合成代谢治疗。
Nat Med. 2012 Jan 29;18(2):307-14. doi: 10.1038/nm.2617.
2
Complete subunit architecture of the proteasome regulatory particle.完整的蛋白酶体调节颗粒亚基结构。
Nature. 2012 Jan 11;482(7384):186-91. doi: 10.1038/nature10774.
3
Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1.Cdh1 通过 APC/C 非依赖性调节 Smurf1 来调控成骨细胞功能。
Mol Cell. 2011 Dec 9;44(5):721-33. doi: 10.1016/j.molcel.2011.09.024.
4
ATP-dependent steps in the binding of ubiquitin conjugates to the 26S proteasome that commit to degradation.ATP 依赖的泛素缀合物与 26S 蛋白酶体结合的步骤，这些步骤决定了降解的命运。
Mol Cell. 2010 Nov 24;40(4):671-81. doi: 10.1016/j.molcel.2010.11.002.
5
Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome.RPN10 的单泛素化调节底物向蛋白酶体的招募。
Mol Cell. 2010 Jun 11;38(5):733-45. doi: 10.1016/j.molcel.2010.05.001.
6
Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by stabilizing the E3 ligase MDM2.Smad 泛素化调节因子 1/2（Smurf1/2）通过稳定 E3 连接酶 MDM2 促进 p53 降解。
J Biol Chem. 2010 Jul 23;285(30):22818-30. doi: 10.1074/jbc.M110.126920. Epub 2010 May 18.
7
N-terminal PH domain and C-terminal auto-inhibitory region of CKIP-1 coordinate to determine its nucleus-plasma membrane shuttling.CKIP-1 的 N 端 PH 结构域和 C 端自抑制区协同决定其核-质膜穿梭。
FEBS Lett. 2010 Mar 19;584(6):1223-30. doi: 10.1016/j.febslet.2010.02.036. Epub 2010 Feb 18.
8
Molecular mechanisms of proteasome assembly.蛋白酶体组装的分子机制。
Nat Rev Mol Cell Biol. 2009 Feb;10(2):104-15. doi: 10.1038/nrm2630.
9
Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1.通过CKIP-1激活靶向HECT型泛素连接酶Smurf1的WW结构域连接区。
Nat Cell Biol. 2008 Aug;10(8):994-1002. doi: 10.1038/ncb1760. Epub 2008 Jul 20.
10
Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction.泛素通过一种新型的普列克底物蛋白同源结构域相互作用停靠在蛋白酶体上。
Nature. 2008 May 22;453(7194):548-52. doi: 10.1038/nature06924.
Zotero 插件