| 货号 | 4602T |
| 反应种属 | Human, |
| 来源宿主 | Rabbit |
| 应用 | WB |
| 目标/特异性 | DNA-PKcs Antibody detects endogenous levels of DNA-PKcs protein. |
| 使用方法 | WB(1:1000) |
| 供应商 | CST |
| 灵敏度 | Endogenous |
| 背景 | DNA-dependent protein kinase (DNA-PK) is an important factor in the repair of double stranded breaks in DNA. Cells lacking DNA-PK or in which DNA-PK is inhibited fail to show proper non-homologous end-joining (NHEJ) (1-7). DNA-PK is composed of two DNA-binding subunits (Ku70 and Ku86) and one 450kDa catalytic subunit (DNA-PKcs) (8). It is thought that a heterodimer of Ku70 and Ku86 binds to double-stranded DNA broken ends before DNA-PKcs binds and is activated (1, 9). Activated DNA-PKcs is a serine/threonine kinase that has been shown to phosphorylate a number of proteins in vitro, including p53, transcription factors, RNA polymerase, and Ku70/Ku86 (10, 11). DNA-PKcs autophosphorylation at multiple sites, including threonine 2609, results in an inactivation of DNA-PK kinase activity and NHEJ ability (12, 13). It has been demonstrated, however, that DNA-PK preferentially phosphorylates substrates before it autophosphorylates, suggesting that DNA-PK autophosphorylation may play a role in disassembly of the DNA repair machinery (14, 15). Autophosphorylation at threonine 2609 has also been shown to be required for DNA-PK mediated double strand break repair, and phosphorylated DNA-PK co-localizes with H2A.X and 53BP1 at sites of DNA damage (16).DNA依赖性蛋白激酶(DNA-PK)是DNA双链断裂修复的一个重要因子。细胞缺少DNA-PK或DNA-PK被抑制都不能进行合适的非同源末端连接(NHEJ) (1-7)。DNA-PK由两个DNA结合亚基(Ku70 和Ku86)和一个450kDa的催化亚基(DNA-PKcs)组成(8)。据认为Ku70和Ku86组成的异源二聚体先于DNA-PKcs及其激活结合DNA双链断裂末端 (1, 9)。激活的DNA-PKcs是一种丝氨酸/苏氨酸激酶，能够体外激活一系列蛋白如p53，转录因子，RNA 聚合酶和Ku70/Ku86 (10, 11)。DNA-PKcs多位点的自体磷酸化，包括2609位苏氨酸，可导致DNA-PK激酶活性和NHEJ能力失活(12, 13)。然而，据发现DNA-PK在自体磷酸化之前可优先磷酸化其底物，表明DNA-PK可能在DAN修复机制中的解聚过程发挥作用(14, 15)。第2609位苏氨酸的磷酸化参与DNA-PK介导的双链断裂修复，而且磷酸化的DNA-PK伴随H2A.X和53BP1集中于DNA损伤位点(16)。 |
| 存放说明 | -20C |
| 计算分子量 | 450 |
| 参考文献 | 1 . Gottlieb, T.M. and Jackson, S.P. (1993) Cell 72, 131-42. 2 . Hartley, K. O. et al. (1995) Cell 82, 840-856. 3 . Rosenzweig, K.E. et al. (1997) Clin Cancer Res 3, 1149-56. 4 . Jackson, S.P. and Jeggo, P.A. (1995) Trends Biochem Sci 20, 412-5. 5 . Roth, D.B. et al. (1995) Curr Biol 5, 496-9. 6 . Baumann, P. and West, S.C. (1998) Proc Natl Acad Sci U S A 95, 14066-70. 7 . Chen, S. et al. (2001) J Biol Chem 276, 24323-30. 8 . Jeggo, P.A. (1997) Mutat Res 384, 1-14. 9 . Suwa, A. et al. (1994) Proc Natl Acad Sci U S A 91, 6904-8. 10 . Anderson, C.W. and Lees-Miller, S.P. (1992) Crit Rev Eukaryot Gene Expr 2, 283-314. 11 . Kuhn, A. et al. (1995) Genes Dev 9, 193-203. 12 . Chan, D.W. and Lees-Miller, S.P. (1996) J Biol Chem 271, 8936-41. 13 . Douglas, P. et al. (2002) Biochem. J. 368, 243-251. 14 . Lees-Miller, S.P. et al. (1992) Mol Cell Biol 12, 5041-9. 15 . Jackson, S.P. et al. (1990) Cell 63, 155-65. 16 . Chan, D.W. et al. (2002) Genes Dev 16, 2333-8. 17 . Yajima, H. et al. (2009) J Mol Biol 385, 800-10. |
Western blot analysis of extracts from M059K (DNA-PK wildtype) and M059J (DNA-PK deficient) cells, using DNA-PK Antibody. |
