| 货号 | 12719S |
| 描述 | SignalSilence® Vitamin D3 Receptor siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit vitamin D3 receptor expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products from CST are rigorously tested in-house and have been shown to reduce target protein expression by western analysis.CST SignalSilence® Vitamin D3 Receptor siRNA I允许研究者使用RNA干扰技术特定地抑制维生素D3受体的表达，使用这种方法可以将双链RNA分子转至细胞内，选择性沉默基因的表达。所有CST SignalSilence® siRNA产品都经过严格的内部测试，并用western方法检测证明可以降低靶蛋白的表达。Quality Control |
| 反应种属 | Human |
| 应用 | TFN |
| 供应商 | CST |
| 背景 | Although originally identified based on their roles in calcium and bone homeostasis, the vitamin D3 receptor (VDR/NR1I1) and its ligand 1-α, 25-dihydroxycholecalciferol [1α, 25(OH)2D3] are now recognized to exert biological effects in almost every tissue of the human body. Targets for vitamin D signaling include the central nervous system, skin, immune system, endocrine glands, kidney, and colon. At the cellular level, vitamin D signaling affects proliferation, differentiation, and apoptosis of both normal and transformed cells. Within the steroid receptor gene family, VDR belongs to the NR1I subfamily that also includes NR1I2/PXR and NR1I3/CAR. The human VDR gene is composed of 11 exons that encode six domains (A-F) of the full length VDR protein, which includes an N-terminal dual zinc finger DNA binding domain, a C-terminal ligand-binding activity domain, and an extensive unstructured region that links the two functional domains together (1). Upon 1α, 25(OH)2D3 binding to the hormone ligand-binding domain, VDR is stabilized by the phosphorylation of Ser51 in the DNA-binding domain by PKC (2), and Ser208 in the hinge region by casein kinase II (3). VDR associates with the retinoic acid receptor (RXR) through dimerization domains. The 1α, 25(OH)2D3-VDR-RXR complex binds to the vitamin D response elements (VDREs) in the promoters of target genes through the DNA-binding domain. Ligand-induced conformation changes in VDR results in the dissociation of the co-repressor, silencing-mediator for retinoid and thyroid hormone receptors (SMRT), and allows interaction of the VDR activation function (AF2) transactivation domain with transcriptional coactivators (1). Studies have shown that variable VDR expression is associated with different forms or stages of cancer and likely results from tissue-type variation in 1α, 25(OH)2D3 signaling. In the case of colon cancer, research indicates that VDR expression is relatively higher in hyperplastic colon polyps and during early tumorigenesis but diminishes in later stage, poorly differentiated tumors. Multiple studies suggest that 1α, 25(OH)2D3 may be an attractive target for development as a therapeutic anticancer agent (4,5) .虽然最初根据维生素D3受体在钙和骨稳态中的作用对其进行认定，但现在在人体几乎每个组织中，维生素D3受体（VDR/NR1I1）及其配体1-α，25 - 二羟胆钙化醇[1α，25（OH）2D3]发挥的生物效应被识别。维生素D的信号靶标包括中枢神经系统、皮肤、免疫系统、内分泌腺体、肾和结肠。在细胞水平上，维生素D信号影响正常和转化细胞的增殖、分化和凋亡。类固醇受体基因家族中，VDR属于NR1I亚科，该亚科还包括NR1I2/PXR和NR1I3/CAR。人维生素D受体基因由编码全长VDR蛋白6个域（AF）的11个外显子组成，其中包括一个N-末端的双锌指结构DNA结合域，一个C-末端配体结合活性域和广泛链接这两个功能域的非结构化区域（1）。1α，25（OH）2D3结合激素配体结合域，由PKC磷酸化DNA结合结构域的丝氨酸（51位）（2）和酪蛋白激酶II磷酸化铰链区的丝氨酸（208位）（3），使VDR稳定。VDR与维甲酸受体（RXR）通过二聚化联合。 1α，25（OH）2D3 VDR-RXR复合物结合维生素D3响应元件(VDREs)通过DNA结合结构域启动靶基因。VDR中配体诱导的构象变化，导致辅阻遏物、维甲酸和甲状腺激素受体沉默介质(SMRT)的降解，并允许VDR活化功能转录激活域（AF2）与转录共激活因子的相互作用（1）。研究表明，可变VDR的表达与癌症不同类型或阶段有关，这可能是由1α, 25(OH)2D3信号中组织类型的变异造成的。研究表明，在结肠癌的情况下，VDR在增生性结肠息肉和早期肿瘤中表达相对较高，但在以后的阶段和低分化肿瘤中表达减少。多项研究表明，1α，25（OH）2D3可能是作为一种治疗型抗癌药物开发有吸引力的靶点（4,5）。 |
| 存放说明 | -20C |
| 参考文献 | Haussler, M.R. et al. (1998) J Bone Miner Res 13, 325-49. Hsieh, J.C. et al. (1991) Proc Natl Acad Sci U S A 88, 9315-9. Jurutka, P.W. et al. (1993) J Biol Chem 268, 6791-9. Matusiak, D. et al. (2005) Cancer Epidemiol Biomarkers Prev 14, 2370-6. Deeb, K.K. et al. (2007) Nat Rev Cancer 7, 684-700. |
Western blot analysis of extracts from 293T cells, transfected with 100 nM SignalSilence® Control siRNA (Unconjugated) #6568 (-) or SignalSilence® Vitamin D3 Receptor siRNA I (+), using Vitamin D3 Receptor (D2K6W) Rabbit mAb #12550 (upper) or GAPDH (D16H11) XP® Rabbit mAb #5174 (lower). The Vitamin D3 Receptor (D2K6W) Rabbit mAb confirms silencing of vitamin D3 receptor expression, while the GAPDH (D16H11) XP® Rabbit mAb is used as a loading control.Western blot方法检测293T细胞提取物，细胞用100 nM SignalSilence® Control siRNA(非结合的) #6568 (-)或SignalSilence® Glucocorticoid Receptor siRNA I (+)转染，使用的抗体为Glucocorticoid Receptor (D8H2) XP® Rabbit mAb #3660(上图)或GAPDH (D16H11) XP® Rabbit mAb #5174 (下图). 证实Glucocorticoid Receptor (D8H2) XP® Rabbit mAb可以沉默糖皮质激素受体的表达，而GAPDH (D16H11) XP® Rabbit mAb 被用作内参。 |
