人乳头瘤病毒5型E6癌蛋白通过与SMAD3结合来抑制转化生长因子β信号通路。
Human papillomavirus type 5 E6 oncoprotein represses the transforming growth factor beta signaling pathway by binding to SMAD3.
作者信息
Mendoza Jose-Andres, Jacob Yves, Cassonnet Patricia, Favre Michel
机构信息
Unité postulante de Génétique, Papillomavirus et Cancer Humain, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex, France.
出版信息
J Virol. 2006 Dec;80(24):12420-4. doi: 10.1128/JVI.02576-05. Epub 2006 Oct 4.
Abstract
Mechanisms of cellular transformation associated with human papillomavirus type 5 (HPV5), which is responsible for skin carcinomas in epidermodysplasia verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid screening and molecular and cellular biology experiments, we found that HPV5 oncoprotein E6 interacts with SMAD3, a key component in the transforming growth factor beta1 (TGF-beta1) signaling pathway. HPV5 E6 inhibits SMAD3 transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF-beta1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.
摘要
与5型人乳头瘤病毒（HPV5）相关的细胞转化机制目前仍知之甚少，该病毒可导致疣状表皮发育不良（EV）患者患皮肤癌。通过酵母双杂交筛选以及分子和细胞生物学实验，我们发现HPV5癌蛋白E6与SMAD3相互作用，SMAD3是转化生长因子β1（TGF-β1）信号通路的关键组成部分。HPV5 E6通过破坏SMAD3/SMAD4复合物的稳定性并诱导这两种蛋白质的降解来抑制SMAD3反式激活。有趣的是，非致癌性EV HPV9的E6蛋白未能与SMAD3相互作用，这表明TGF-β1信号通路的下调可能是HPV5皮肤癌发生的一个决定因素。
相似文献
1
Human papillomavirus type 5 E6 oncoprotein represses the transforming growth factor beta signaling pathway by binding to SMAD3.人乳头瘤病毒5型E6癌蛋白通过与SMAD3结合来抑制转化生长因子β信号通路。
J Virol. 2006 Dec;80(24):12420-4. doi: 10.1128/JVI.02576-05. Epub 2006 Oct 4.
2
Human papillomavirus type 18 E6 protein binds the cellular PDZ protein TIP-2/GIPC, which is involved in transforming growth factor beta signaling and triggers its degradation by the proteasome.人乳头瘤病毒18型E6蛋白与细胞PDZ蛋白TIP-2/GIPC结合，该蛋白参与转化生长因子β信号传导，并触发其被蛋白酶体降解。
J Virol. 2005 Apr;79(7):4229-37. doi: 10.1128/JVI.79.7.4229-4237.2005.
3
TGF-beta activated Smad signalling leads to a Smad3-mediated down-regulation of DSPP in an odontoblast cell line.转化生长因子-β激活的Smad信号通路导致成牙本质细胞系中Smad3介导的牙本质涎磷蛋白下调。
Arch Oral Biol. 2004 Nov;49(11):911-8. doi: 10.1016/j.archoralbio.2004.05.005.
4
Kaposi's sarcoma-associated herpesvirus viral IFN regulatory factor 1 inhibits transforming growth factor-beta signaling.卡波西肉瘤相关疱疹病毒的病毒干扰素调节因子1抑制转化生长因子-β信号传导。
Cancer Res. 2005 Mar 1;65(5):1738-47. doi: 10.1158/0008-5472.CAN-04-2374.
5
Cutaneous HPV8 and MmuPV1 E6 Proteins Target the NOTCH and TGF-β Tumor Suppressors to Inhibit Differentiation and Sustain Keratinocyte Proliferation.皮肤型人乳头瘤病毒8型（Cutaneous HPV8）和小家鼠乳头瘤病毒1型（MmuPV1）的E6蛋白靶向NOTCH和转化生长因子-β（TGF-β）肿瘤抑制因子，以抑制分化并维持角质形成细胞增殖。
PLoS Pathog. 2017 Jan 20;13(1):e1006171. doi: 10.1371/journal.ppat.1006171. eCollection 2017 Jan.
6
TLP, a novel modulator of TGF-beta signaling, has opposite effects on Smad2- and Smad3-dependent signaling.TLP是一种新型的TGF-β信号调节剂，对Smad2和Smad3依赖性信号传导具有相反的作用。
EMBO J. 2003 Sep 1;22(17):4465-77. doi: 10.1093/emboj/cdg428.
7
Differences in Smad4 expression in human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck squamous cell carcinoma.16型人乳头瘤病毒阳性与16型人乳头瘤病毒阴性头颈部鳞状细胞癌中Smad4表达的差异
Clin Cancer Res. 2005 May 1;11(9):3191-7. doi: 10.1158/1078-0432.CCR-04-1299.
8
Cyclic adenosine 3',5'-monophosphate-elevating agents inhibit transforming growth factor-beta-induced SMAD3/4-dependent transcription via a protein kinase A-dependent mechanism.环磷酸腺苷升高剂通过蛋白激酶A依赖性机制抑制转化生长因子-β诱导的SMAD3/4依赖性转录。
Oncogene. 2003 Dec 4;22(55):8881-90. doi: 10.1038/sj.onc.1206871.
9
Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1.靶向SMAD4缺陷型人胰腺癌细胞中的内源性转化生长因子β受体信号传导可抑制其侵袭性表型1。
Cancer Res. 2004 Aug 1;64(15):5200-11. doi: 10.1158/0008-5472.CAN-04-0018.
10
Reduced Smad3 protein expression and altered transforming growth factor-beta1-mediated signaling in cystic fibrosis epithelial cells.囊性纤维化上皮细胞中Smad3蛋白表达降低及转化生长因子-β1介导的信号传导改变。
Am J Respir Cell Mol Biol. 2001 Dec;25(6):732-8. doi: 10.1165/ajrcmb.25.6.4574.
引用本文的文献
1
Molecular mechanisms of human papilloma virus related skin cancers: A review.人乳头瘤病毒相关皮肤癌的分子机制：综述。
Medicine (Baltimore). 2024 May 24;103(21):e38202. doi: 10.1097/MD.0000000000038202.
2
Exploring type I interferon pathway: virulent vs. attenuated strain of African swine fever virus revealing a novel function carried by MGF505-4R.探索 I 型干扰素途径：非洲猪瘟病毒的强毒株与弱毒株揭示了由 MGF505-4R 携带的新功能。
Front Immunol. 2024 Mar 11;15:1358219. doi: 10.3389/fimmu.2024.1358219. eCollection 2024.
3
Host-Specific Interplay between Foot-and-Mouth Disease Virus 3D Polymerase and the Type-I Interferon Pathway.口蹄疫病毒 3D 聚合酶与 I 型干扰素通路的宿主特异性相互作用。
Viruses. 2023 Mar 1;15(3):666. doi: 10.3390/v15030666.
4
Comparative Virus-Host Protein Interactions of the Bluetongue Virus NS4 Virulence Factor.比较蓝舌病病毒 NS4 毒力因子的病毒-宿主蛋白相互作用。
Viruses. 2022 Jan 19;14(2):182. doi: 10.3390/v14020182.
5
Effects of β-HPV on DNA damage response pathways to drive carcinogenesis: a review.β-HPV 对 DNA 损伤反应通路的影响驱动致癌作用：综述。
Virus Genes. 2021 Feb;57(1):23-30. doi: 10.1007/s11262-020-01813-w. Epub 2021 Jan 3.
6
Effective combinatorial immunotherapy for penile squamous cell carcinoma.阴茎鳞状细胞癌的有效组合免疫疗法。
Nat Commun. 2020 May 1;11(1):2124. doi: 10.1038/s41467-020-15980-9.
7
BetaHPV E6 and E7 colocalize with NuMa in dividing keratinocytes.β人乳头瘤病毒E6和E7在分裂的角质形成细胞中与核有丝分裂器蛋白共定位。
Virus Genes. 2019 Oct;55(5):600-609. doi: 10.1007/s11262-019-01685-9. Epub 2019 Jul 9.
8
Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway.新型蓝舌病毒 NS3 蛋白在调节 MAPK/ERK 信号通路中的新功能。
J Virol. 2019 Jul 30;93(16). doi: 10.1128/JVI.00336-19. Print 2019 Aug 15.
9
Manipulation of Epithelial Differentiation by HPV Oncoproteins.HPV 致癌蛋白对上皮细胞分化的调控。
Viruses. 2019 Apr 22;11(4):369. doi: 10.3390/v11040369.
10
本文引用的文献
1
Hepatitis C virus core variants isolated from liver tumor but not from adjacent non-tumor tissue interact with Smad3 and inhibit the TGF-beta pathway.从肝肿瘤而非相邻非肿瘤组织中分离出的丙型肝炎病毒核心变体与Smad3相互作用并抑制TGF-β信号通路。
Oncogene. 2005 Sep 8;24(40):6119-32. doi: 10.1038/sj.onc.1208749.
2
Kaposi's sarcoma-associated herpesvirus viral IFN regulatory factor 1 inhibits transforming growth factor-beta signaling.卡波西肉瘤相关疱疹病毒的病毒干扰素调节因子1抑制转化生长因子-β信号传导。
Cancer Res. 2005 Mar 1;65(5):1738-47. doi: 10.1158/0008-5472.CAN-04-2374.
3
Human papillomaviruses and skin cancer.人乳头瘤病毒与皮肤癌。
J Clin Virol. 2005 Mar;32 Suppl 1:S67-71. doi: 10.1016/j.jcv.2004.11.018.
4
Mechanisms of human papillomavirus-induced oncogenesis.人乳头瘤病毒诱导肿瘤发生的机制。
J Virol. 2004 Nov;78(21):11451-60. doi: 10.1128/JVI.78.21.11451-11460.2004.
5
Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation.丙型肝炎病毒蛋白与Smad3相互作用，并差异调节转化生长因子β/ Smad3介导的转录激活。
Oncogene. 2004 Oct 14;23(47):7821-38. doi: 10.1038/sj.onc.1208066.
6
New insights into TGF-beta-Smad signalling.转化生长因子-β-信号转导通路的新见解。
Trends Biochem Sci. 2004 May;29(5):265-73. doi: 10.1016/j.tibs.2004.03.008.
7
TFIIH transcription factor, a target for the Rift Valley hemorrhagic fever virus.TFIIH转录因子，裂谷热病毒的一个靶点。
Cell. 2004 Feb 20;116(4):541-50. doi: 10.1016/s0092-8674(04)00132-1.
8
Identification of a gadd45beta 3' enhancer that mediates SMAD3- and SMAD4-dependent transcriptional induction by transforming growth factor beta.鉴定一个gadd45β 3'增强子，其通过转化生长因子β介导SMAD3和SMAD4依赖性转录诱导。
J Biol Chem. 2004 Feb 13;279(7):5278-87. doi: 10.1074/jbc.M311517200. Epub 2003 Nov 20.
9
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.转化生长因子-β（TGF-β）从细胞膜到细胞核的信号传导机制。
Cell. 2003 Jun 13;113(6):685-700. doi: 10.1016/s0092-8674(03)00432-x.
10
Chapter 8: Human papillomavirus and skin cancer.第8章：人乳头瘤病毒与皮肤癌。
J Natl Cancer Inst Monogr. 2003(31):52-6. doi: 10.1093/oxfordjournals.jncimonographs.a003483.
Zotero 插件