SnoN的基本特征、生物学功能及其在肝纤维化中的作用

刘瑞霞; 齐海宇; 王婧; 阴赪宏

SnoN的基本特征、生物学功能及其在肝纤维化中的作用

首都医科大学附属北京友谊医院感染暨急救医学科

基金项目:

国家自然科学基金(8107313)；中国肝炎防治基金会王宝恩肝纤维化研究基金(20090042)；

详细信息

中图分类号: R575.2
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出版历程
- 出版日期: 2012-09-20

Characteristics, function, and role of SnoN in liver fibrosis

Research funding:

摘要

摘要: SnoN是一种核转录共抑制因子,在细胞核和细胞浆中均能阻断TGFβ1/Smad信号转导,是该信号通路的重要负调控因子之一。SnoN在肝纤维化发生发展中的作用已有研究报道,并日益引起人们的关注。因此,本文回顾了有关SnoN方面的研究进展,对其基本特征、生物学功能及其在肝纤维化中的作用作一综述。
- SnoN /
- 肝硬化 /
- 转化生长因子β /
- Smad蛋白质类
Abstract: The Smad transcriptional co-repressor ski-related novel protein N (SnoN) is an important negative regulator of the tumor growth factor-beta 1 (TGFβ1) /Smad signaling cascade.The SnoN protein can repress Smad-mediated transactivation of TGFβ target genes in the nucleus and cytoplasm of cells.TGFβ1 is a well-characterized profibrotic cytokine that is believed to play a crucial role in tissue fibrogenesis in a wide range of organs.Extensive studies have suggested that TGFβ1 is one of the most important factors mediating the onset and progression of various fibrotic diseases.Recently, SnoN has been shown to reduce liver fibrosis in rat models.In this review, we discuss the recent progress in understanding SnoN characteristics, function, and role in liver fibrosis.
- SnoN /
- liver cirrhosis /
- transforming growth factor beta /
- smad proteins

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参考文献(33)

[1]Stroschein SL, Wang W, Zhou S, et al.Negative feedbackregulation of TGF-beta signaling by the SnoN oncoprotein[J].Science, 1999, 286 (5440) :771-774.

[2]Nomura N, Sasamoto S, Ishii S, et al.Isolation of humancDNA clones of ski and the ski-related gene, sno[J].Nu-cleic Acids Res, 1989, 17 (14) :5489-5500.

[3]Pearson-White S.SnoI, a novel alternatively spliced iso-form of the ski protooncogene homolog, sno[J].NucleicAcids Res, 1993, 21 (19) :4632-4638.

[4]Huynh MA, Ikeuchi Y, Netherton S, et al.An isoform-spe-cific SnoN1-FOXO1 repressor complex controls neuronalmorphogenesis and positioning in the mammalian brain[J].Neuron, 2011, 69 (5) :930-944.

[5]Nanjundan M, Cheng KW, Zhang F, et al.Overexpressionof SnoN/SkiL, amplified at the 3q26.2 locus, in ovariancancers:a role in ovarian pathogenesis[J].Mol Oncol, 2008, 2 (2) :164-181.

[6]Jahchan NS, Luo KX.SnoN in mammalian development, functionand diseases[J].Curr Opin Pharmacol, 2010, 10 (6) :670-675.

[7]Luo K.Ski and SnoN:negative regulators of TGF-beta sig-naling[J].Curr Opin Genet Dev, 2004, 14 (1) :65-70.

[8]Krakowski AR, Laboureau J, Mauviel A, et al.Cytoplasmic SnoNin normal tissues and nonmalignant cells antagonizes TGF-betasignaling by sequestration of the Smad proteins[J].Proc NatlAcad Sci USA, 2005, 102 (35) :12437-12442.

[9]Cohen SB, Zheng G, Heyman HC, et al.Heterodimers ofthe SnoN and Ski oncoproteins form preferentially over ho-modimers and are more potent transforming agents[J].Nucleic Acids Res, 1999, 27 (4) :1006-1014.

[10]Akagi I, Miyashita M, Makino H, et al.SnoN overexpressionis predictive of poor survival in patients with esophagealsquamous cell carcinoma[J].Ann Surg Oncol, 2008, 15 (10) :2965-2975.

[11]Zhang Y, Yao W, Qiu J, et al.The involvement of down-regulation of Cdh1-APC in hippocampal neuronal apoptosisafter global cerebral ischemia in rat[J].Neurosci Lett, 2011, 505 (2) :71-75.

[12]Stegmuller J, Huynh MA, Yuan Z, et al.TGF beta-Smad2 sig-naling regulates the Cdh1-APC/SnoN pathway of axonal mor-phogenesis[J].J Neurosci, 2008, 28 (8) :1961-1969.

[13]Bonni S, Wang HR, Causing CG, et al.TGF-beta inducesassembly of a Smad2-Smurf2 ubiquitin ligase complex thattargets SnoN for degradation[J].Nat Cell Biol, 2001, 3 (6) :587-595.

[14]Miyazono K, Koinuma D.Arkadia-beyond the TGF-βpath-way[J].J Biochem, 2011, 149 (1) :1-3.

[15]Va’zquez-Macl A, Rufz-Mendoza AB, Fonseca-Sa’nchezMA, et al.Downregulation of Ski and SnoN co-repressors byanisomycin[J].FEBS Lett, 2005, 579 (17) :3701-3706.

[16]Tan RY, He WC, Lin X, et al.Molecular basis for the cell typespecific induction of SnoN expression by hepatocyte growth fac-tor[J].J Am Soc Nephrol, 2007, 18 (8) :2340-2349.

[17]Esposito C, Parrilla B, Cornacchia F, et al.The antifibrogeniceffect of hepatocyte growth factor (HGF) on renal tubular (HK-2) cells is dependent on cell growth[J].Growth Fac-tors, 2009, 27 (3) :173-180.

[18]Luo DD, Phillips A, Fraser D.Bone morphogenetic protein-7 inhibits proximal tubular epithelial cell Smad3 signaling viaincreased SnoN expression[J].Am J Pathol, 2010, 176 (3) :1139-1147.

[19]Deheuninck J, Luo KX.Ski and SnoN, potent negative regu-lators of TGF-beta signaling[J].Cell Res, 2009, 19 (1) :47-57.

[20]Wegner K, Bachmann A, Schad JU, et al.Dynamics andfeedback loops in the transforming growth factor beta signa-ling pathway[J].Biophys Chem, 2012, 162:22-34.

[21]Javelaud D, van Kempen L, Alexaki VI, et al.Mauviel A.Ef-ficient TGF-β/SMAD signaling in human melanoma cells as-sociated with high c-SKI/SnoN expression[J].Mol Canc-er, 2011, 10 (1) :2.

[22]Lamouille S, Derynck R.Oncogene and tumour suppressor:the two faces of SnoN[J].EMBO J, 2009, 28 (22) :3459-3460.

[23]Wrighton KH, Liang M, Bryan B, et al.Transforming growth fac-tor-beta-independent regulation of myogenesis by SnoN su-moylation[J].J Biol Chem, 2007, 282 (9) :6517-6524.

[24]Pot I, Bonni S.SnoN in TGF-beta signaling and cancer biol-ogy[J].Curr Mol Med, 2008, 8 (4) :319-328.

[25]Netherton SJ, Bonni S.Suppression of TGF-β-inducedepithelial-mesenchymal transition like phenotype by aPIAS1 regulated sumoylation pathway in NMuMG epithelialcells[J].PLoS One, 2010, 5 (11) :e13971.

[26]Yang JW, Zhang XH, Li YJ, et al.Down regulation of Smadtranscriptional corepressors SnoN and Ski in the fibrotic kid-ney:an amplification mechanism for TGF-beta1 signaling[J].J Am Soc Nephrol, 2003, 14 (12) :3167-3177.

[27]刘瑞霞, 郭兵, 崔龙, 等.SnoN蛋白在糖尿病大鼠肾组织中的表达及其意义[J].中国病理生理杂志, 2008, 24 (6) :1188-1192.

[28]刘瑞霞, 郭兵, 肖瑛, 等.SnoN和Smad2/3信号蛋白与糖尿病大鼠肾小管-间质纤维化的关系[J].基础医学与临床, 2010, 30 (9) :944-951.

[29]刘瑞霞, 郭兵, 肖瑛, 等.糖尿病大鼠肾组织Smurf2表达及其与SnoN蛋白降解的关系[J].中国病理生理杂志, 2010, 26 (9) :1743-1748.

[30]刘瑞霞, 郭兵, 王圆圆, 等.SnoN对高糖诱导大鼠原代肾小管上皮细胞纤维连结蛋白合成的影响[J].中国病理生理杂志, 2011, 27 (10) :1931-1937.

[31]Marquez-Aguirre A, Sandoval-Rodriguez A, Gonzalez-Cue-vas J, et al.Adenoviral delivery of dominant-negative transfor-ming growth factor beta type II receptor up-regulates tran-scriptional repressor SKI-like oncogene, decreases matrix met-alloproteinase 2 in hepatic stellate cell and prevents liver fibrosisin rats[J].J Gene Med, 2009, 11 (3) :207-219.

[32]Martínez-Rizo A, Bueno-Topete M, González-Cuevas J, et al.Plasmin plays a key role in the regulation of profibro-genic molecules in hepatic stellate cells[J].Liver Int, 2010, 30 (2) :298-310.

[33]Cai Y, Shen XZ, Zhou CH, et al.Abnormal expression ofSmurf2 during the process of rat liver fibrosis[J].Chin JDig Dis, 2006, 7 (4) :237-245.

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