泛素-蛋白酶体系统与核因子κB的激活：泛素连接酶KPC1在p105加工及肿瘤抑制中的作用
The ubiquitin-proteasome system and activation of NF-κB: involvement of the ubiquitin ligase KPC1 in p105 processing and tumor suppression.
作者信息
Kravtsova-Ivantsiv Yelena, Ciechanover Aaron
机构信息
The David and Janet Polak Cancer and Vascular Biology Research Center; The Rappaport Faculty of Medicine and Research Institute; Technion - Israel Institute of Technology ; Haifa, Israel.
出版信息
Mol Cell Oncol. 2015 May 26;2(4):e1054552. doi: 10.1080/23723556.2015.1054552. eCollection 2015 Oct-Dec.
Abstract
The p50 subunit of nuclear factor-kappa B (NF-κB) is generated from processing of the p105 precursor. We identified KIP1 ubiquitination-promoting complex 1 (KPC1) as the ubiquitin (Ub) ligase mediating this process. Overexpression of KPC1 results in tumor suppression, probably due to the generation of p50-p50 homodimers. It appears that high levels of KPC1 and nuclear p50 are important for maintaining the non-malignant state.
摘要
核因子-κB（NF-κB）的p50亚基由p105前体加工产生。我们鉴定出KIP1泛素化促进复合物1（KPC1）为介导此过程的泛素（Ub）连接酶。KPC1的过表达导致肿瘤抑制，可能是由于p50-p50同型二聚体的产生。似乎高水平的KPC1和核p50对维持非恶性状态很重要。
相似文献
1
The ubiquitin-proteasome system and activation of NF-κB: involvement of the ubiquitin ligase KPC1 in p105 processing and tumor suppression.泛素-蛋白酶体系统与核因子κB的激活：泛素连接酶KPC1在p105加工及肿瘤抑制中的作用
Mol Cell Oncol. 2015 May 26;2(4):e1054552. doi: 10.1080/23723556.2015.1054552. eCollection 2015 Oct-Dec.
2
A short binding site in the KPC1 ubiquitin ligase mediates processing of NF-κB1 p105 to p50: A potential for a tumor-suppressive PROTAC.KPC1 泛素连接酶中的一个短结合位点介导 NF-κB1 p105 向 p50 的加工：一种潜在的肿瘤抑制性 PROTAC。
Proc Natl Acad Sci U S A. 2021 Dec 7;118(49). doi: 10.1073/pnas.2117254118.
3
KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth.KPC1 介导的 NF-κB1 p105 泛素化和蛋白酶体加工限制肿瘤生长。
Cell. 2015 Apr 9;161(2):333-47. doi: 10.1016/j.cell.2015.03.001.
4
The NF-ĸB p50 subunit generated by KPC1-mediated ubiquitination and limited proteasomal processing, suppresses tumor growth.由KPC1介导的泛素化和有限的蛋白酶体加工产生的NF-κB p50亚基可抑制肿瘤生长。
Cancer Cell Int. 2023 Apr 13;23(1):67. doi: 10.1186/s12935-023-02919-5.
5
The p105 NF-ĸB precursor is a pseudo substrate of the ubiquitin ligase FBXO7, and its binding to the ligase stabilizes it and results in stimulated cell proliferation.p105 NF-κB 前体是泛素连接酶 FBXO7 的伪底物，它与连接酶的结合稳定了连接酶，并导致细胞增殖受到刺激。
Biochem Biophys Res Commun. 2021 Jun 18;558:224-230. doi: 10.1016/j.bbrc.2020.08.098. Epub 2020 Sep 12.
6
A20 inhibits both the degradation and limited processing of the NF-κB p105 precursor: A novel additional layer to its regulator role.A20抑制NF-κB p105前体的降解和有限加工：其调节作用的一个新的附加层面。
Biochem Biophys Res Commun. 2017 Nov 4;493(1):52-57. doi: 10.1016/j.bbrc.2017.09.075. Epub 2017 Sep 18.
7
The Tumor Suppressor Functions of Ubiquitin Ligase KPC1: From Cell-Cycle Control to NF-κB Regulator.泛素连接酶 KPC1 的肿瘤抑制功能：从细胞周期控制到 NF-κB 调节剂。
Cancer Res. 2023 Jun 2;83(11):1762-1767. doi: 10.1158/0008-5472.CAN-22-3739.
8
Excess of the NF-ĸB p50 subunit generated by the ubiquitin ligase KPC1 suppresses tumors via PD-L1- and chemokines-mediated mechanisms.泛素连接酶 KPC1 产生的 NF-κB p50 亚基过剩通过 PD-L1 和趋化因子介导的机制抑制肿瘤。
Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29823-29831. doi: 10.1073/pnas.2019604117. Epub 2020 Nov 9.
9
The A-to-I editing of KPC1 promotes intrahepatic cholangiocarcinoma by attenuating proteasomal processing of NF-κB1 p105 to p50.KPC1 的 A-to-I 编辑通过减弱 NF-κB1 p105 向 p50 的蛋白酶体加工来促进肝内胆管癌。
J Exp Clin Cancer Res. 2022 Dec 8;41(1):338. doi: 10.1186/s13046-022-02549-1.
10
NFKB1: a suppressor of inflammation, ageing and cancer.NFKB1：炎症、衰老和癌症的抑制因子。
FEBS J. 2016 May;283(10):1812-22. doi: 10.1111/febs.13627. Epub 2016 Jan 13.
引用本文的文献
1
Proteasome-derived peptides: separating the trash from the recycling.蛋白酶体衍生肽：区分垃圾与回收物。
Trends Biochem Sci. 2025 Jul 12. doi: 10.1016/j.tibs.2025.06.007.
2
The Role of the Ubiquitin System in Eye Diseases.泛素系统在眼部疾病中的作用。
Life (Basel). 2025 Mar 20;15(3):504. doi: 10.3390/life15030504.
3
Enhancing gut microbiota and microbial function with inulin supplementation in children with obesity.补充菊粉可改善肥胖儿童的肠道微生物群和微生物功能。
Int J Obes (Lond). 2024 Dec;48(12):1696-1704. doi: 10.1038/s41366-024-01590-8. Epub 2024 Jul 20.
4
Deubiquitylating Enzyme OTUB1 Facilitates Neuronal Survival After Intracerebral Hemorrhage Via Inhibiting NF-κB-triggered Apoptotic Cascades.去泛素化酶 OTUB1 通过抑制 NF-κB 触发的凋亡级联反应促进脑出血后的神经元存活。
Mol Neurobiol. 2024 Mar;61(3):1726-1736. doi: 10.1007/s12035-023-03676-2. Epub 2023 Sep 29.
5
Parvimonas micra infection enhances proliferation, wound healing, and inflammation of a colorectal cancer cell line.微小帕毛单胞菌感染增强结直肠癌细胞系的增殖、伤口愈合和炎症反应。
Biosci Rep. 2023 Jun 28;43(6). doi: 10.1042/BSR20230609.
6
Upregulated Proteasome Subunits in COVID-19 Patients: A Link with Hypoxemia, Lymphopenia and Inflammation.COVID-19 患者中上调的蛋白酶体亚基：与低氧血症、淋巴细胞减少和炎症有关。
Biomolecules. 2022 Mar 13;12(3):442. doi: 10.3390/biom12030442.
7
CD95/Fas suppresses NF-κB activation through recruitment of KPC2 in a CD95L/FasL-independent mechanism.CD95/Fas通过一种不依赖CD95L/FasL的机制募集KPC2来抑制NF-κB激活。
iScience. 2021 Dec 1;24(12):103538. doi: 10.1016/j.isci.2021.103538. eCollection 2021 Dec 17.
8
Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1.小檗碱作为 G 蛋白偶联雌激素受体 1 的激动剂抑制 MDA-MB-231 细胞。
Int J Mol Sci. 2021 Oct 24;22(21):11466. doi: 10.3390/ijms222111466.
9
Carfilzomib Enhances the Suppressive Effect of Ruxolitinib in Myelofibrosis.卡非佐米增强芦可替尼在骨髓纤维化中的抑制作用。
Cancers (Basel). 2021 Sep 28;13(19):4863. doi: 10.3390/cancers13194863.
10
Anti-Inflammatory Activity of 4-((1,2)-3-Hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol Isolated from Maxim. in LPS-Stimulated RAW 264.7 Macrophages and Zebrafish Larvae Model.从Maxim.中分离得到的4-((1,2)-3-羟基-1-(4-羟基苯基)-1-甲氧基丙-2-基)-2-甲氧基苯酚在脂多糖刺激的RAW 264.7巨噬细胞和斑马鱼幼虫模型中的抗炎活性
Pharmaceuticals (Basel). 2021 Aug 6;14(8):771. doi: 10.3390/ph14080771.
本文引用的文献
1
KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth.KPC1 介导的 NF-κB1 p105 泛素化和蛋白酶体加工限制肿瘤生长。
Cell. 2015 Apr 9;161(2):333-47. doi: 10.1016/j.cell.2015.03.001.
2
Linear ubiquitin chains: NF-κB signalling, cell death and beyond.线性泛素链：NF-κB 信号转导、细胞死亡及其他。
Nat Rev Mol Cell Biol. 2014 Aug;15(8):503-8. doi: 10.1038/nrm3836. Epub 2014 Jul 9.
3
Diverse roles of the ubiquitin system in NF-κB activation.泛素系统在核因子κB激活中的多种作用。
Biochim Biophys Acta. 2014 Jan;1843(1):129-36. doi: 10.1016/j.bbamcr.2013.03.011. Epub 2013 Mar 21.
4
NF-κB and the link between inflammation and cancer.NF-κB 与炎症和癌症之间的联系。
Immunol Rev. 2012 Mar;246(1):379-400. doi: 10.1111/j.1600-065X.2012.01099.x.
5
The diverse and complex roles of NF-κB subunits in cancer.NF-κB 亚基在癌症中的多样化和复杂作用。
Nat Rev Cancer. 2012 Jan 19;12(2):121-32. doi: 10.1038/nrc3204.
6
Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis.IkappaB激酶复合物对NF-κB1 p105丝氨酸927位点的直接磷酸化对于信号诱导的p105蛋白水解至关重要。
J Biol Chem. 2001 Jun 22;276(25):22215-22. doi: 10.1074/jbc.M101754200. Epub 2001 Apr 10.
7
Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated ubiquitination and degradation for the NF-kappaB precursor p105 and IkappaBalpha.IκB激酶诱导的SCF（βTrCP）介导的NF-κB前体p105和IκBα泛素化及降解的共享途径。
Mol Cell Biol. 2001 Feb;21(4):1024-35. doi: 10.1128/MCB.21.4.1024-1035.2001.
8
SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase.SCF（β）（-TrCP）泛素连接酶介导的NF-κB p105加工需要IκB激酶对其C末端进行磷酸化。
EMBO J. 2000 Jun 1;19(11):2580-91. doi: 10.1093/emboj/19.11.2580.
9
Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105. Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein, E2, and a novel ubiquitin-protein ligase, E3, involved in conjugation.泛素介导的核因子-κB转录激活因子前体p105的加工。无细胞系统的重建以及参与缀合反应的泛素载体蛋白E2和新型泛素-蛋白连接酶E3的鉴定。
J Biol Chem. 1995 Sep 15;270(37):21707-14. doi: 10.1074/jbc.270.37.21707.
10
Generation of p50 subunit of NF-kappa B by processing of p105 through an ATP-dependent pathway.
Nature. 1991 Dec 5;354(6352):395-8. doi: 10.1038/354395a0.
Zotero 插件