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FHL2通过相互作用抑制分化抑制蛋白家族成员的转录抑制活性 被引量：1

FHL2 Cooperates with Id Family Proteins and Inhibits Their Transcriptional Repression Activities
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摘要 目的:探讨FHL2与Id(分化抑制蛋白)家族蛋白之间的相互作用及FHL2对Id蛋白功能的调控效应。方法:用GST-pulldown与免疫共沉淀(CoIP)方法检测FHL2与Id家族蛋白成员之间在体内外的相互作用;用共转染与报告基因驱动的萤光素酶方法检测FHL2对Id蛋白介导转录抑制效应的调控作用。结果:FHL2与Id家族的4个蛋白均存在直接的相互作用关系,表位分析结果显示FHL2蛋白中的第2个LIM结构域在FHL2/Id相互作用中是必需的,Id蛋白N端结构域在介导FHL2/Id相互作用中是必需的,FHL2/Id相互作用不依赖于Id蛋白中的螺旋-环-螺旋结构;通过相互作用,FHL2阻止了Id蛋白对碱性螺旋-环-螺旋转录因子E47转录活性的抑制作用。结论:FHL2是一个新识别的Id蛋白广谱的相互作用因子,通过对Id蛋白功能活性的抑制效应,FHL2可能参与Id介导的多种生物学效应以及肿瘤发生与进展。 Objective： To investigate the interaction of FHL2 and Id（inhibitor of differentiation） family components and the functional effect of FHL2 on Id2-mediated transcriptional repression. Methods： The interaction of FHL2 and Id family components was measured by GST-pulldoawn and coimmunoprecipitation assays. The regulatory effect of FHL2 on Id proteins-mediated transcriptional repression was determined by cotransfection and luciferase assays. Results：FHL2 directly interacts with all members of Id family, which does not depend on the existence of the helix-loop-helix（HLH） domain con- served within Id proteins. The second LIM domain containing in FHL2 or the N-terminal region in Id proteins are essential for the direct binding of FHL2 and Id proteins. FHL2 represses the inhibitory effect of Id proteins on E47, a ubiquitously expressed basic HLH transcriptional factor, -mediated transcriptional activity. Conclusion： FHL2 is a novel interacting factor of Id proteins. Through cooperating with Id proteins and sequentially repressing their function, FHL2 may involve in the multiple biological effects and tumorogenesis mediated by Id proteins.
作者 韩为东 赵亚力 伍志强 司艺玲 杨洁 田丽媛 孟元光
机构地区 解放军总医院基础医学研究所 解放军总医院妇产科
出处 《生物技术通讯》 CAS 2008年第6期791-794,共4页 Letters in Biotechnology
基金 国家自然科学基金(30870507) 解放军总医院苗圃基金(07MP69)
关键词 FHL2 分化抑制蛋白 相互作用 抑制子 FHL2 inhibitor of differentiation interaction repressor
分类号 Q78 [生物学—分子生物学] Q25 [生物学—细胞生物学]
  • 相关文献

参考文献15

  • 1Massari M E, Murre C. Helix-loop-helix proteins: Regulators of transcription in eucaryotic organisms[J]. Mol Cell Biol, 2000,20(2): 429-440.
  • 2Ruzinova M B, Benezra R. Id proteins in development, cell cycle and cancer[J]. Trends Cell Biol, 2003,13(8):410-418.
  • 3Fraidenraich D, Stillwell E, Romero E, et al. Rescue of cardiac defects in Id knock out embryos by injection of embroynoic stem cells[J]. Science, 2004,306(5649):247-252.
  • 4Iavarone I, Lasorella A. ID proteins as targets in cancer and tools in neurobiology[J]. Trends Mol Med, 2006,12(12):588-594.
  • 5Perk J, lavarone A, Benezra R. Id family of helix-loop-helix proteins in cancer[J]. Nat Rev Cancer, 2005,5(8):603-614.
  • 6Johannessena M, Mollera S, Hansena T, et al. The multifunctional roles of the four-and-a-half-LIM only protein FHL2 [J]. Cell Mol Life Sci, 2006,63(3):268-284.
  • 7Yan J, Zhu J, Zhong H, et al. BRCA1 interacts with FHL2 and enhances FHL2 transactivation function[J]. FEBS Lett, 2003,553(1- 2):183-189.
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  • 9伍志强,孟元光,赵亚力,杨洁,田丽媛,司艺玲,韩为东.HLH缺失型Id2候选相互作用蛋白[J].军事医学科学院院刊,2007,31(4):317-321. 被引量：5
  • 10Lasorella A, Iavarone A. The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system[J]. Proc Natl Acad Sci USA, 2006,103(3):4976-4981.

二级参考文献22

  • 1Benezra R,Davis RL,Lockshon D,et al.The protein Id:a negative regulator of helix-loop-helix DNA binding proteins[J].Cell,1990,61(1):49-59.
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  • 4Perk J,Iavarone A,Benezra R.Id Family of helix-loop-helix proteins in cancer[J].Nat Rev Cancer,2005,5(8):603-614.
  • 5Lasorella A,Iavarone A.The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system[J].Proc Natl Acad Sci USA,2006,103(13):4976-4981.
  • 6Kurooka H,Yokota Y.Nucleo-cytoplasmic shuttling of Id2,a negative regulator of basic helix-loop-helix transcription factors[J].J Biol Chem,2005,280(6):4313-4320.
  • 7Wang S,Sdrulla A,Johnson JE,et al.A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development[J].Neuron,2001,29(3):603-614.
  • 8Lasorella A,Stegmüller J,Guardavaccaro D,et al.Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth[J].Nature,2006,442(7101):471-474.
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共引文献4

同被引文献9

  • 1Massari ME,Murre C. Helix-loop-helix proteins: Regulators of transcription in eucaryotic organisms. Mol Cell Biol, 2000, 20(2):429
  • 2Ruzinova MB, Benezra R. Id proteins in development, cell cycle and cancer. Trends Cell Biol, 2003, 13(8) :410
  • 3Perk J, Iavarone A, Benezra R. Id family of helix- loop-helix proteins in cancer. Nature Rev Cancer, 2005, 5(8): 603
  • 4Swarbrick A, Akerfeldt MC, Lee CS, et al. Regulation of cyelin expression and cell cycle progression in breast epithelial cells by the helix-loop-helix protein Idl. Oncogene, 2005, 24(3) :381
  • 5Gupta GP, Perk J, Acharyya S, et al. ID genes mediate tumor reintiation during breast cancer lung metastasis. Proc Natl Acad Sci USA, 2007, 104 (49) : 19506
  • 6Iavarone I, Lasorella A. ID proteins as targets in cancer and tools in neurobiology. Trends Mol Med, 2006, 12(12): 588
  • 7Johannessena M, Mollera S, Hansena T, et al. The multifunctional roles of the four-and-a-half-LIM only protein FHL2. Cell Mol Life Sci, 2006, 63(3) :268
  • 8Jang KS, Han HX, Paik SS, et al. Id-1 overexpression in invasive ductal carcinoma cells is significantly associated with intraturnoral microvessel density in ER-negative/node-positive breast cancer. Cancer Lett, 2006, 244(2) :203
  • 9韩为东,赵亚力,伍志强,司艺玲,杨洁,田丽媛,孟元光.FHL2通过相互作用抑制Id2的功能活性[J].中国生物化学与分子生物学报,2008,24(9):810-817. 被引量：2

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生物技术通讯
2008年 第6期

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