期刊文献+

利用四环素调控系统研究CHIP对TGF-β信号通路的抑制性调节 被引量:2

Tetracycline Controlled CHIP Expression Inhibits TGF-β Signal Pathway
下载PDF
导出
摘要 为了研究伴侣分子相互作用蛋白CHIP对TGF-β信号通路的调控,利用四环素基因表达调控系统,建立四环素调控表达CHIP的稳定细胞系(Mv1Lu-Tetoff-CHIP).利用此细胞模型,发现CHIP的过量表达可显著降低细胞内Smad2/3蛋白水平;荧光素酶报告分析也表明开启CHIP蛋白表达可明显降低Smads介导的基因转录活性;进一步的免疫印迹结果显示CHIP蛋白可明显下调TGF-β所诱导的下游基因JunB的表达.上述结果提示CHIP可以作为一种新的蛋白质分子抑制性调节TGF-β信号通路. To investigate the regulatory function of chaperone interacting protein CHIP in TGF-β signal pathway, a tetracycline induced CHIP expression stable cell line (Mv1Lu-Tet off-CHIP) was generated. In this cell line model, it was observed that overexpression of CHIP dramatically reduced the endougenous Smad2/3 protein level. Luciferase reporter analysis showed that CHIP inhibited the Smads induced transcription activity. Furthermore, Western blot results indicated that CHIP could downregulate gene expression of JunB, a quick response gene induced by TGF-β. These results provided new evidences that CHIP might be a novel signal protein negatively regulating TGF-β signal pathway.
出处 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2005年第6期557-561,共5页 Progress In Biochemistry and Biophysics
基金 国家自然科学基金资助项目(30470888) 国家重点基础研究发展规划项目(973)(2001CB510006 2002CB51300) 裕元基金资助项目(20240005-06)~~
关键词 四环素调控 CHIP TGF-Β SMAD2/3 JUNB 抑制 tetracycline control, CHIP, transforming growth factor-β (TGF-β), Smad2/3, JunB, inhibition
  • 相关文献

参考文献21

  • 1张平,王金泉.转化生长因子-β族信号的转导[J].生物化学与生物物理进展,2000,27(4):375-378. 被引量:8
  • 2Massague J, Blain S W, Lo R S. TGF-β signaling in growth control,cancer, and heritable disorders. Cell, 2000,103:295-309. 被引量:1
  • 3Ballinger C A, Connell P, Wu Y, et al. Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.Mol Cell Bid, 1999,19(6):4535-4545. 被引量:1
  • 4Li L Y, Xin H, Xu X L, et al. CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription. Mol cell Biol, 2004,24(2):856-864. 被引量:1
  • 5徐夏莲,辛宏,李林钰,张慧,黄海长,常智杰.Hsp/Hsc70相互作用蛋白CHIP在大鼠肾纤维化组织中的高表达[J].中国生物化学与分子生物学报,2004,20(3):347-351. 被引量:2
  • 6徐夏莲,辛宏,王春华,王银银,常智杰.序列特异的双链RNA可解除CHIP对TGF-β信号通路的抑制作用[J].中国生物化学与分子生物学报,2004,20(4):445-450. 被引量:2
  • 7Xin H, Xu X L, Li L Y, et al. CHIP controls the sensitivity of TGF-signaling by maintaining the basal level of Smad3 through ubiquitin-mediated degradation. J Biol Chem,2005,280 (21):20842-20850. 被引量:1
  • 8Shen X,Hu P P,Liberati N T,et al.TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol Biol Cell, 1998, 9:3309-3319. 被引量:1
  • 9Akiyoshi S, Inoue H, Hanai J, et al. c-Ski acts a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with Smads. J Biol Chem,1999, 274:35269-35277. 被引量:1
  • 10Bonni S, Wang H R, Causing C G, et al. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol, 2001, 3:587-595. 被引量:1

二级参考文献39

  • 1[1]Ballinger C A, Connell P, Wu Y, Hu Z, Thompson L J, Yin L Y,Patterson C. Identification of CHIP, a novel teteratricopeptide repeatcontaining protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol, 1999,19(6) :4535 ~ 4545 被引量:1
  • 2[2]Connell P, Ballinger C A, Jiang J, Wu T, Thompson L J, Hohfeld J,Patterson C. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol,2001,3( 1 ) :93 ~ 96 被引量:1
  • 3[3]Meaeham G C, Patterson C, Zhang W, Younger J M, Cyr D M. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol,2001,3( 1 ): 100 ~ 105 被引量:1
  • 4[4]Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama K,Takahashi R. CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity.Mol Cell, 2002,10: 55 ~ 67 被引量:1
  • 5[5]Li L Y, Xin H, Xu X L, Huang M, Zhang X J, Chen Y, Zhang S P, Fu X Y, Chang Z J. CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription. Mol Cell Biol, 2004,24(2): 856 ~ 864 被引量:1
  • 6[6]Wells R G. Fibrogenesis: TGF-β signaling pathways. Am J Physiol Gastrointest Physiol, 2000,279: G845 ~ G850 被引量:1
  • 7[7]Marty G, Browning D D, Ye R D. Identification of tetratricopeptide repeatl as an adaptor protein that interacts with heterotrimeric G proteins and the small GSTase. Mol Cell Biol, 2003,23:3847 ~ 3858 被引量:1
  • 8[8]Brychzy A, Rein T, Winklhofer K F, Hartl F U, Young J C, Obermann W M. Cofactor Tpr2 combines two TPR domains and a J domain to regulate the HspT0/Hsp90 chaperone system. EMBO J,2003,22:3611 ~3623 被引量:1
  • 9[9]Jiang J, Ballinger C A, Wu Y, Dai Q, Cyr D M, Hohfeld J, Patterson C.CHIP is a U-box-dependent E3 ubiquitin ligase. J Biol Chem, 2001,276: 42938 ~ 42944 被引量:1
  • 10[10]Xu W, Marcu M, Yuan X, Mimnaugh E, Patterson C, Neckers L.Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for e-ErbB2/Neu. Proc Natl Acad Sci USA, 2002,99: 12847 ~12852 被引量:1

共引文献9

同被引文献24

  • 1Lauriane Fritsch,Luis A Martinez,et al.Conditional gene knock-down by CRE-dependent short interfering RNAs.EMBO reports,2004,5(2):178~182 被引量:1
  • 2Yang W,Pnsehen W.Conditional gene silencing in mammalian cells mediated by a stress-inducible promoter.BBRC,2008,365 (3):521~527 被引量:1
  • 3Zhang J,Wang C,Ke N,et al.A more efficient RNAi inducible system for tight regulation of gene expression in mammalian cells and xenograft animals.RNA,2007,13(8):1375~1385 被引量:1
  • 4Chang H S,Lin C H,Chen Y C,et al.Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown.Am J Pathol,2004,165(5):1535~1541 被引量:1
  • 5Seidler B,Schmidt A,Mayr U,et al.A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown in vivo by using avian retroviral vectors.Proc Natl Acad Sci USA,2008,105(29):10137~10142 被引量:1
  • 6Kilby N J,Snaith M R,Murray J A.Site-specific recombinases:tools for genome engineering.Trends Genet,1993,9(12):413~421 被引量:1
  • 7Dymecki S M.FLP recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenie mice.Proc Natl Acad Sci USA,1996,93(12):6191~6196 被引量:1
  • 8Nspoll C A,Lemteux C,Jorgensen R.Introduction of a chimeric cha2 conne synthetase gene in Petunia results in reversible cosuppression of homologous genes in trans.Plant Cell,1990,2(4):279~289 被引量:1
  • 9Guo S,Kemphues K J.Par-1,a gene required for establishing polarity in Caenorhabdities elegans embryos,encodes a putative Set/Thr kinase that is asymmetrically distributed.Cell,1995,81 (4):611~620 被引量:1
  • 10Fire A,XU S,Montgomerym K,et al.Potent and specific genetic interference by double stranded RNA in Caenorhabdities elegans.Nature,1998,391(6669):806~811 被引量:1

引证文献2

二级引证文献6

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部