期刊文献+

DNA-PK蛋白功能及其调控机制 被引量:3

DNA-PK Function and Regulatory Mechanism
原文传递
导出
摘要 DNA依赖性蛋白激酶(DNA-dependent protein kinase,DNA-PK)是由3个亚基组成的丝/苏氨酸蛋白激酶,属于磷脂酰肌醇-3激酶相关激酶家族(phosphatidylinositol 3-kinase-related kinases,PIKK),是基因组DNA损伤修复过程中的关键蛋白激酶,参与并决定着非同源末端连接DNA损伤修复通路的整个进程.此外DNA-PK还参与了电离辐射诱导的凋亡信号转导通路,免疫细胞V(D)J重组、免疫细胞分化、胰岛素刺激下的细胞应答等过程,具有维持端粒稳定性的功能.DNA-PK活性的升高会降低肿瘤对放射的敏感性,其活性主要受自身磷酸化调控,此外活性氧、EGFR、MG132抑制剂、PP1γ1和PP5等蛋白磷酸酶也有调控DNA-PK活性的作用. DNA-dependent protein kinase ( DNA-PK), a serine/threonine kinase consisting of three subunits, is a member of the PIKKs (phosphoinositide 3-kinase-like family of protein kinases) . DNA-PK is the key protein kinase in the genomic DNA damage repair, participating in and determining the whole process of non-homologous end-joining. Furthermore, DNA-PK is involved in ionizing radiation stimulated apoptotie signal transduction, V (D) J recombination, immune cell differentiation, insulin-stimulated cellular responses, and maintenance of telomere stabili- ty. Increase of DNA-PK activity reduces the sensitivity of tumors to radiation. The activity of DNA-PK is mainly regulated by its autophosphorylation. Reactive oxygen species, EGFR, MG132 inhibitor, and protein phosphatase such as PP1 T1 PP5 also play a role in control of DNA-PK activity.
出处 《医学分子生物学杂志》 CAS CSCD 2011年第3期278-282,共5页 Journal of Medical Molecular Biology
  • 相关文献

参考文献39

  • 1COLLIS S J,DEWEESE T L,JEGGO P A,et al.The life and death of DNA-PK[J].Oncogene,2005,24(6):949-961.
  • 2FALCK J,COATES J,JACKSON S P.Conserved modes of recruitment of ATM,ATR and DNA-PKcs to sites of DNA damage[J].Nature,2005,434(7033):605-611.
  • 3GELL D,JACKSON S P.Mapping of protein-protein interactions within the DNA-dependent protein kinase complex[J].Nucleic Acids Res,1999,27(17):3494-3502.
  • 4SINGLETON B K,TORRES-ARZAYUS M I,ROTTINGHAUS S T,et al.The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit[J].Mol Cell Biol,1999,19(5):3267-3277.
  • 5HAMMARSTEN O,CHU G.DNA-dependent protein kinase:DNA binding and activation in the absence of Ku[J].Proc Natl Acad Sci USA,1998,95(2):525-530.
  • 6JAYARAM S,KETNER G,ADACHI N,et al.Loss of DNA ligase IV prevents recognition of DNA by double-strand break repair proteins XRCC4 and XLF[J].Nucleic Acids Res,2008,36(18):5773-5786.
  • 7CUI X,YU Y,GUPTA S,et al.Autophosphorylation of DNA-dep-endent protein kinase regulates DNA end processing and may also alter double-strand break repair pathway choice[J].Mol Cell Biol,2005,25(24):10842-10852.
  • 8DING Q,REDDY Y V,WANG W,et al.Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair[J].Mol Cell Biol,2003,23(16):5836-5848.
  • 9BUDMAN J,CHU G.Processing of DNA for nonhomologous end-joining by cell-free extract[J].EMBO J,2005,24(4):849-860.
  • 10SPAGNOLO L,RIVERA-CALZADA A,PEARL L H,et al.Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair[J].Mol Cell,2006,22(4):511-519.

同被引文献34

  • 1高国兰,万红英,黄传生,邹学森,陈文学.P-gp、GST-π、TS蛋白在宫颈癌中的表达及临床意义[J].临床肿瘤学杂志,2007,12(1):23-26. 被引量:11
  • 2Lee K J,Lin Y F,Chou H Y,et al.Involvement of DNA-dependent protein kinase in normal cellcycleprogression through mitosis[J].J Biol Chem,2011,286(14):12796-12802.
  • 3Hsu F M,Zhang S,Chen B P.Role of DNA-dependent protein kinasecatalytic subunit in cancerdevelopment and treatment[J].Transl Cancer Res,2012,1 (1):22-34.
  • 4Seo S B,Hur J G,Kim M J,et al.TRAIL sensitize MDR cells to MDR-related drugs by down-regulation of P-glycoprotein through inhibition of DNA-PKcs/Akt/GSK-3beta pathway and activation of caspases[J].Mol Cancer,2010,28 (9):199.
  • 5Lee P C,Lee H J,Kakadiya R,et al.Multidrug-resistant cells over expressing P-glycoprotein are susceptible to DNA crosslinking agents due to attenuated Src/nuclear EGFR cascade-activated DNA repair activity[J].Oncogene,2013,32(9):1144-1154.
  • 6Bouwman P,Jonkers J.The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance[J].Nat Rev Cancer,2012,12 (9):587-598.
  • 7Curtin N J.DNA repair dysregulation from cancer driver to therapeutic target[J].Nat Rev Cancer,2012,12(12):801-817.
  • 8Rothkamm K,Krüger I,Thompson L H,et al.Pathways of DNA double-strand break repair during the mammalian cell cycle[J].Mol Cell Biol,2003,23(16):5706-5715.
  • 9Evert M,Frau M,Tomasi M L,et al.Deregulation of DNA-dependent protein kinase catalytic subunit contributes to human hepatocarcino genesis development and has a putative prognostic value[J].Br J Cancer,2013,109(10):2654-2664.
  • 10Cornell L,Munck J,Curtin N,et al.PTU-0420 DNA-PKor ATM inhibition inhibits non-homologous end joining and enhances chemo-and radio sensitivity in hepatocellular cancer cell lines[J].Gut,2012,61:A201.

引证文献3

二级引证文献11

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