Fbx4基因的突变会抑制SCF(Fbx4)连接酶的二聚化，并导致人类癌症中细胞周期蛋白D1的过表达。
Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.
作者信息
Barbash Olena, Zamfirova Petia, Lin Douglas I, Chen Xiangmei, Yang Ke, Nakagawa Hiroshi, Lu Fengmin, Rustgi Anil K, Diehl J Alan
机构信息
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
出版信息
Cancer Cell. 2008 Jul 8;14(1):68-78. doi: 10.1016/j.ccr.2008.05.017.
Abstract
SCF(Fbx4) was recently identified as the E3 ligase for cyclin D1. We now describe cell-cycle-dependent phosphorylation and dimerization of Fbx4 that is regulated by GSK3beta and is defective in human cancer. We present data demonstrating that a pathway involving Ras-Akt-GSK3beta controls the temporal phosphorylation and dimerization of the SCF(Fbx4) E3 ligase. Inhibition of Fbx4 activity results in accumulation of nuclear cyclin D1 and oncogenic transformation. The importance of this regulatory pathway for normal cell growth is emphasized by the prevalence of mutations in Fbx4 in human cancer that impair dimerization. Collectively, these data reveal that inactivation of the cyclin D1 E3 ligase likely contributes to cyclin D1 overexpression in a significant fraction of human cancer.
摘要
SCF(Fbx4)最近被鉴定为细胞周期蛋白D1的E3连接酶。我们现在描述Fbx4的细胞周期依赖性磷酸化和二聚化，其受GSK3β调控且在人类癌症中存在缺陷。我们提供的数据表明，一条涉及Ras-Akt-GSK3β的信号通路控制着SCF(Fbx4) E3连接酶的瞬时磷酸化和二聚化。抑制Fbx4活性会导致核内细胞周期蛋白D1积累和致癌转化。人类癌症中Fbx4的突变普遍存在，这些突变会损害二聚化，这凸显了该调控通路对正常细胞生长的重要性。总体而言，这些数据表明，细胞周期蛋白D1 E3连接酶的失活可能在很大一部分人类癌症中导致细胞周期蛋白D1的过表达。
相似文献
1
Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.Fbx4基因的突变会抑制SCF(Fbx4)连接酶的二聚化，并导致人类癌症中细胞周期蛋白D1的过表达。
Cancer Cell. 2008 Jul 8;14(1):68-78. doi: 10.1016/j.ccr.2008.05.017.
2
Phosphorylation-dependent regulation of SCF(Fbx4) dimerization and activity involves a novel component, 14-3-3ɛ.磷酸化依赖的 SCF（Fbx4）二聚体和活性的调节涉及一种新的成分，即 14-3-3ɛ。
Oncogene. 2011 Apr 28;30(17):1995-2002. doi: 10.1038/onc.2010.584. Epub 2011 Jan 17.
3
The Fbx4 tumor suppressor regulates cyclin D1 accumulation and prevents neoplastic transformation.Fbx4 肿瘤抑制因子调节细胞周期蛋白 D1 的积累，防止肿瘤转化。
Mol Cell Biol. 2011 Nov;31(22):4513-23. doi: 10.1128/MCB.05733-11. Epub 2011 Sep 12.
4
Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex.SCF（FBX4-αB晶状体蛋白）复合物介导的细胞周期蛋白D1的磷酸化依赖性泛素化
Mol Cell. 2006 Nov 3;24(3):355-66. doi: 10.1016/j.molcel.2006.09.007.
5
SCF(Fbx4/alphaB-crystallin) E3 ligase: when one is not enough.SCF（Fbx4/αB-晶状体蛋白）E3 连接酶：当一个不够用时。
Cell Cycle. 2008 Oct;7(19):2983-6. doi: 10.4161/cc.7.19.6775. Epub 2008 Oct 12.
6
Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.鉴定破坏细胞周期蛋白D1磷酸化依赖性核输出的突变。
Oncogene. 2006 Oct 12;25(47):6291-303. doi: 10.1038/sj.onc.1209644. Epub 2006 May 29.
7
A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells.噻唑烷二酮类药物促进癌细胞中细胞周期蛋白D1蛋白酶体降解的一种新机制。
J Biol Chem. 2008 Sep 26;283(39):26759-70. doi: 10.1074/jbc.M802160200. Epub 2008 Jul 23.
8
FBX4 mediates rapid cyclin D1 proteolysis upon DNA damage in immortalized esophageal epithelial cells.FBX4 介导永生化食管上皮细胞中 DNA 损伤时细胞周期蛋白 D1 的快速蛋白水解。
Biochem Biophys Res Commun. 2021 May 21;554:76-82. doi: 10.1016/j.bbrc.2021.03.089. Epub 2021 Mar 27.
9
Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation.赖氨酸 269 对于细胞周期蛋白 D1 被 SCF（Fbx4/αB-晶状体蛋白）连接酶泛素化以及随后的蛋白酶体依赖性降解是必需的。
Oncogene. 2009 Dec 10;28(49):4317-25. doi: 10.1038/onc.2009.287.
10
Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase.SCF(Fbx4)泛素连接酶依赖二聚化的泛素化的结构基础。
J Biol Chem. 2010 Apr 30;285(18):13896-906. doi: 10.1074/jbc.M110.111518. Epub 2010 Feb 24.
引用本文的文献
1
A tetracycline-inducible Split TurboID system for specific biotinylation and identification of nuclear proteins from HEK293T cells.一种用于特异性生物素化和鉴定来自HEK293T细胞的核蛋白的四环素诱导型分裂TurboID系统。
Turk J Biol. 2025 Jan 6;49(2):162-174. doi: 10.55730/1300-0152.2734. eCollection 2025.
2
The Urinary Concentration of Trefoil Factor 3 (TFF3) in the Term and Preterm Neonates.足月儿和早产儿尿液中三叶因子3（TFF3）的浓度
J Clin Med. 2023 Jul 27;12(15):4936. doi: 10.3390/jcm12154936.
3
Targeting cyclin D1 as a therapeutic approach for papillary thyroid carcinoma.将细胞周期蛋白D1作为甲状腺乳头状癌的一种治疗方法。
Front Oncol. 2023 Jun 22;13:1145082. doi: 10.3389/fonc.2023.1145082. eCollection 2023.
4
E3 ligase MG53 suppresses tumor growth by degrading cyclin D1.E3 连接酶 MG53 通过降解细胞周期蛋白 D1 抑制肿瘤生长。
Signal Transduct Target Ther. 2023 Jul 7;8(1):263. doi: 10.1038/s41392-023-01458-9.
5
USP13 deubiquitinates and stabilizes cyclin D1 to promote gastric cancer cell cycle progression and cell proliferation.USP13 通过去泛素化和稳定 cyclin D1 来促进胃癌细胞周期进程和细胞增殖。
Oncogene. 2023 Jul;42(29):2249-2262. doi: 10.1038/s41388-023-02739-x. Epub 2023 Jun 13.
6
Tumor suppressor mediated ubiquitylation of hnRNPK is a barrier to oncogenic translation.肿瘤抑制因子介导的 hnRNPK 的泛素化是致癌翻译的障碍。
Nat Commun. 2022 Nov 3;13(1):6614. doi: 10.1038/s41467-022-34402-6.
7
The E3 Ubiquitin Ligase Fbxo4 Functions as a Tumor Suppressor: Its Biological Importance and Therapeutic Perspectives.E3泛素连接酶Fbxo4作为一种肿瘤抑制因子：其生物学重要性及治疗前景
Cancers (Basel). 2022 Apr 25;14(9):2133. doi: 10.3390/cancers14092133.
8
Targeting CDK4 and CDK6 in cancer.针对癌症中的 CDK4 和 CDK6。
Nat Rev Cancer. 2022 Jun;22(6):356-372. doi: 10.1038/s41568-022-00456-3. Epub 2022 Mar 18.
9
Molecular analysis of cyclin D1 modulators PRKN and FBX4 as candidate tumor suppressors in sporadic parathyroid adenomas.细胞周期蛋白D1调节因子PRKN和FBX4作为散发性甲状旁腺腺瘤候选肿瘤抑制因子的分子分析
Endocr Connect. 2021 Mar;10(3):302-308. doi: 10.1530/EC-21-0055.
10
LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer.长链非编码 RNA DILA1 抑制细胞周期蛋白 D1 的降解，促进乳腺癌对他莫昔芬的耐药性。
Nat Commun. 2020 Nov 2;11(1):5513. doi: 10.1038/s41467-020-19349-w.
本文引用的文献
1
Nuclear accumulation of cyclin D1 during S phase inhibits Cul4-dependent Cdt1 proteolysis and triggers p53-dependent DNA rereplication.细胞周期蛋白D1在S期的核内积累抑制了Cul4依赖的Cdt1蛋白水解，并触发了p53依赖的DNA再复制。
Genes Dev. 2007 Nov 15;21(22):2908-22. doi: 10.1101/gad.1586007.
2
Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis.细胞周期蛋白D1核输出和蛋白水解的破坏加速乳腺癌变。
Oncogene. 2008 Feb 21;27(9):1231-42. doi: 10.1038/sj.onc.1210738. Epub 2007 Aug 27.
3
FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors.白血病细胞中的FBW7突变介导NOTCH信号通路激活及对γ-分泌酶抑制剂的耐药性。
J Exp Med. 2007 Aug 6;204(8):1813-24. doi: 10.1084/jem.20070876. Epub 2007 Jul 23.
4
The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia.SCFFBW7泛素连接酶复合体作为T细胞白血病中的一种肿瘤抑制因子。
J Exp Med. 2007 Aug 6;204(8):1825-35. doi: 10.1084/jem.20070872. Epub 2007 Jul 23.
5
Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination.SCFCdc4 二聚体的超面取向为底物泛素化提供了多种几何结构。
Cell. 2007 Jun 15;129(6):1165-76. doi: 10.1016/j.cell.2007.04.042.
6
Fbw7/hCDC4 dimerization regulates its substrate interactions.Fbw7/hCDC4二聚化调节其与底物的相互作用。
Cell Div. 2007 Feb 13;2:7. doi: 10.1186/1747-1028-2-7.
7
Characterization of cullin-based E3 ubiquitin ligases in intact mammalian cells--evidence for cullin dimerization.完整哺乳动物细胞中基于cullin的E3泛素连接酶的特性——cullin二聚化的证据
Cell Signal. 2007 May;19(5):1071-80. doi: 10.1016/j.cellsig.2006.12.002. Epub 2006 Dec 16.
8
Fbw7 isoform interaction contributes to cyclin E proteolysis.Fbw7亚型相互作用有助于细胞周期蛋白E的蛋白水解。
Mol Cancer Res. 2006 Dec;4(12):935-43. doi: 10.1158/1541-7786.MCR-06-0253.
9
Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex.SCF（FBX4-αB晶状体蛋白）复合物介导的细胞周期蛋白D1的磷酸化依赖性泛素化
Mol Cell. 2006 Nov 3;24(3):355-66. doi: 10.1016/j.molcel.2006.09.007.
10
Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.鉴定破坏细胞周期蛋白D1磷酸化依赖性核输出的突变。
Oncogene. 2006 Oct 12;25(47):6291-303. doi: 10.1038/sj.onc.1209644. Epub 2006 May 29.
Zotero 插件