SignalSilence? Chk1 siRNA I

• 产品编号：CST-6241S      品牌：CST       原厂货号：6241S
• 产品分类：DNA和RNA纯化 > RNA干扰 > RNAi Oligos > siRNA
• 应用分类：

描述：

Chk1 siRNA I 能够抑制人和猴Chk1表达。研究人员可以使用CST的SignalSilence® Chk1 siRNA I，采用RNA干扰（一种通过传递外源性的双链RNA分子到细胞中从而能选择性的沉默基因表达的方法）技术特异性的抑制Chk1 蛋白表达。CST所有的SignalSilence® siRNA产品都经过了严格的内部测试并采用Western分析证明其可以有效降低靶蛋白的表达。CST推荐使用50 nM Chk1 siRNA转染48-72小时后裂解细胞。Chk1激酶能够充当ATM/ATR激酶的下游并在DNA损伤检验点控制、胚胎发育和肿瘤抑制中发挥重要作用(1)。Chk1的激活涉及317位和345位丝氨酸的磷酸化，其发生响应DNA复制阻滞和某些类型的基因毒性应激反应(2)。尽管345位丝氨酸的磷酸化有助于伴随检验点激活的Chk1定位到核，317位丝氨酸的磷酸化连同位点特异性的PTEN磷酸化允许DNA复制停滞引起的细胞周期折返(4)。Chk1发挥其细胞周期检验点调节机制部分经由调控磷酸酶家族的cdc25。Chk1磷酸化cdc25A后靶向蛋白降解并通过14-3-3的结合抑制自身的活性(5)。激活的chk1能够通过216位丝氨酸的磷酸化失活cdc25C，阻塞cdc2的激活和有丝分裂转换的进入(6)。中心体的chk1被认为可以磷酸化cdc25B并抑制其激活CDK1-cyclin B1，藉此废除有丝分裂纺锤体的形成和染色质凝聚(7)。此外，Chk1通过调节Aurora B和BubR1在纺锤体检验点功能中发挥重要作用(8)。鉴于Chk1的抑制作用能够引起许多肿瘤细胞系的死亡，它已经成为肿瘤治疗中心的药物靶点(9)。Small Interfering RNA (siRNA)被用来特异性沉默多种人类肿瘤细胞系内的chk1蛋白。

1. Liu, Q. et al. (2000) Genes Dev 14, 1448-59.
2. Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
3. Jiang, K. et al. (2003) J Biol Chem 278, 25207-17.
4. Martin, S.A. and Ouchi, T. (2008) Mol Cancer Ther 7, 2509-16.
5. Chen, M.S. et al. (2003) Mol Cell Biol 23, 7488-97.
6. Zeng, Y. et al. (1998) Nature 395, 507-10.
7. Löffler, H. et al. (2006) Cell Cycle 5, 2543-7.
8. Zachos, G. et al. (2007) Dev Cell 12, 247-60.
9. Garber, K. (2005) J Natl Cancer Inst 97, 1026-8.
10. Chen, Z. et al. (2003) Mol. Cancer Ther. 2(6) , 543-548.

原厂资料：

Specificity / Sensitivity

Chk1 siRNA I will inhibit human and monkey Chk1 expression.

Description

SignalSilence® Chk1 siRNA from Cell Signaling Technology allows the researcher to specifically inhibit Chk1 expression using RNA interference, a method in which gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products are rigorously tested in-house and have been shown to reduce protein expression in specified cell lines.

Background

Chk1 kinase acts downstream of ATM/ATR kinase and plays an important role in DNA damage checkpoint control, embryonic development, and tumor suppression (1). Activation of Chk1 involves phosphorylation at Ser317 and Ser345 and occurs in response to blocked DNA replication and certain forms of genotoxic stress (2). While phosphorylation at Ser345 serves to localize Chk1 to the nucleus following checkpoint activation (3), phosphorylation at Ser317 along with site-specific phosphorylation of PTEN allows for reentry into the cell cycle following stalled DNA replication (4). Chk1 exerts its checkpoint mechanism on the cell cycle, in part, by regulating the cdc25 family of phosphatases. Chk1 phosphorylation of cdc25A targets it for proteolysis and inhibits its activity through 14-3-3 binding (5). Activated Chk1 can inactivate cdc25C via phosphorylation at Ser216, blocking the activation of cdc2 and transition into mitosis (6). Centrosomal Chk1 has been shown to phosphorylate cdc25B and inhibit its activation of CDK1-cyclin B1, thereby abrogating mitotic spindle formation and chromatin condensation (7). Furthermore, Chk1 plays a role in spindle checkpoint function through regulation of Aurora B and BubR1 (8). Chk1 has emerged as a drug target for cancer therapy as its inhibition leads to cell death in many cancer cell lines (9).Small Interfering RNA (siRNA) has been used to specifically silence chk1 in various human cancer cell lines (5). 

1. Liu, Q. et al. (2000) Genes Dev 14, 1448-59.
2. Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
3. Jiang, K. et al. (2003) J Biol Chem 278, 25207-17.
4. Martin, S.A. and Ouchi, T. (2008) Mol Cancer Ther 7, 2509-16.
5. Chen, M.S. et al. (2003) Mol Cell Biol 23, 7488-97.
6. Zeng, Y. et al. (1998) Nature 395, 507-10.
7. Löffler, H. et al. (2006) Cell Cycle 5, 2543-7.
8. Zachos, G. et al. (2007) Dev Cell 12, 247-60.
9. Garber, K. (2005) J Natl Cancer Inst 97, 1026-8.
10. Chen, Z. et al. (2003) Mol. Cancer Ther. 2(6) , 543-548.

注意事项：

Storage: Chk1 siRNA is supplied in RNAse-free water. Aliquot
and store at -20°C