DNA-PKcs (3H6) Mouse mAb

• 产品编号：CST-12311S      品牌：CST       原厂货号：12311S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

DNA-PK (3H6) Mouse mAb recognizes endogenous levels of total DNA-PK protein.DNA-PK (3H6)Mouse mAb可以识别内源性DNA-PK (3H6)总蛋白。单克隆抗体由合成肽段免疫动物产生，该肽段与表达在大肠杆菌中的人DNA-PK蛋白一致。DNA依赖蛋白激酶（DNA-PK）是DNA双链损伤修复过程中的重要因子。缺少DNA-PK或DNA-PK被抑制的细胞将无法进行正常的非同源末端连接(NHEJ) (1-7).DNA-PK包含了两个DNA结合亚基（Ku70和Ku86）以及1个450kDa的催化亚基(DNA-PKcs) (8). Ku70和Ku86的异二聚体可以在DNA-PKcs结合前和双链DNA损伤末端结合并激活（1,9）。激活的DNA-PK是一个丝氨酸/苏氨酸激酶可以磷酸化一系列的蛋白，包括p53，转录因子，RNA聚合酶和Ku70/Ku86（10,11）。DNA-PKcs可以在多个位点自磷酸化，包括2609位苏氨酸和2056位丝氨酸，将导致DNA-PK的激酶活性和NHEJ能力丢失（12,13）。但是研究已经证明，DNA-PK在进行自磷酸化前会选择性的磷酸化其底物，这提示了DNA-PK的自磷酸化可能在DNA损伤修复机制中发挥了作用（14,15）。已经发现2609位苏氨酸自磷酸化对DNA-PK介导的双链损伤修复，磷酸化的DNA-PK与H2A.X 和53BP1的共定位在DNA损伤的位点都是必须的（16）。2056位丝氨酸的磷酸化是对双链DNA损伤和ATM激活的应激（17）。

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.

原厂资料：

Specificity / Sensitivity

DNA-PK (3H6) Mouse mAb recognizes endogenous levels of total DNA-PK protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a recombinant protein fragment specific to human DNA-PK protein expressed in E.coli.

Background

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 nonhomologous end-joining (NHEJ) (1-7). DNA-PK is composed of two DNA-binding subunits (Ku70 and Ku86) and one 450 kDa 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 Thr2609 and Ser2056, 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 Thr2609 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). Phosphorylation at Ser2056 occurs in response to double-stranded DNA breaks and ATM activation (17).

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.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody