HIF-1α Antibody

• 产品编号：CST-3716S      品牌：CST       原厂货号：3716S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

HIF-1α抗体识别内源性的HIF-1α总蛋白，此抗体在生理条件下不与其他家族成员交叉反应，也不检测羟基化的HIF-1α.多克隆抗体由合成的肽段免疫动物产生，该肽段与邻近人源HIF-1α蛋白Ser653氨基酸残基序列一致。抗体由肽段由蛋白A和亲和层析技术纯化.

缺氧诱导因子1(HIF1)是一个二聚体转录因子在细胞应激缺氧环境时会发挥作用(1)。HIF1复合物包括两个亚基，HIF-1α和HIF-1β，都属于PAS(Per, ARNT, Sim)碱性螺旋-环-螺旋家族(2)。HIF1调控多种应激缺氧环境的基因，包括调控血管生成，红细胞生成，细胞周期，细胞代谢和细胞凋亡过程的基因。广泛表达的HIF-1α通常是由泛素/蛋白酶体途径迅速在含氧量正常的细胞中降解的。在常氧条件下，HIF-1α被脯氨酸羟基化促进了其被绑定到von Hippel Lindau蛋白(VLH)E3连接酶复合物引起构象变化，随后被泛素化和蛋白酶体降解(3,4)。低氧条件和化学羟化酶抑制剂(如去铁胺和钴)抑制HIF-1α的降解，并增加其蛋白稳定性。此外，HIF-1α可通过各种细胞因子经过PI3K-AKT-mTOR通路诱导进入氧无关的信号通路(5-7)。

HIF-1β由于能够以伴侣方式与芳香烃受体(AHR)结合形成异二聚体复合物，也被称为芳香烃受体核转位(ARNT) (8)。HIF-1β与AhR能够在外源性化学物质代谢中发挥重要作用(8)。除此以外染色体转位导致的TEL-ARNT融合蛋白和急性髓细胞白血病相关(9)。研究也发现ARNT/HIF-1β的表达水平在2型糖尿病人的胰岛内明显表达下降，提示HIF-1β在胰岛β细胞功能过程中发挥作用(10)。

1. Sharp, F.R. and Bernaudin, M. (2004) Nat Rev Neurosci 5, 437-48.
2. Wang, G.L. et al. (1995) Proc Natl Acad Sci U S A 92, 5510-4.
3. Jaakkola, P. et al. (2001) Science 292, 468-72.
4. Maxwell, P.H. et al. (1999) Nature 399, 271-5.
5. Fukuda, R. et al. (2002) J Biol Chem 277, 38205-11.
6. Jiang, B.H. et al. (2001) Cell Growth Differ 12, 363-9.
7. Laughner, E. et al. (2001) Mol Cell Biol 21, 3995-4004.
8. Walisser, J.A. et al. (2004) Proc Natl Acad Sci U S A 101, 16677-82.
9. Salomon-Nguyen, F. et al. (2000) Proc Natl Acad Sci U S A 97, 6757-62.
10. Gunton, J.E. et al. (2005) Cell 122, 337-49.

原厂资料：

Specificity / Sensitivity

HIF-1α Antibody detects endogenous levels of total HIF-1α protein. The antibody does not cross-react with other family members at physiological conditions, and does not detect significant levels of hydroxylated HIF-1α.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser653 of human HIF-1α. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor that plays a critical role in the cellular response to hypoxia (1). The HIF1 complex consists of two subunits, HIF-1α and HIF-1β, which are basic helix-loop-helix proteins of the PAS (Per, ARNT, Sim) family (2). HIF1 regulates the transcription of a broad range of genes that facilitate responses to the hypoxic environment, including genes regulating angiogenesis, erythropoiesis, cell cycle, metabolism, and apoptosis. The widely expressed HIF-1α is typically degraded rapidly in normoxic cells by the ubiquitin/proteasomal pathway. Under normoxic conditions, HIF-1α is proline hydroxylated leading to a conformational change that promotes binding to the von Hippel Lindau protein (VLH) E3 ligase complex; ubiquitination and proteasomal degradation follows (3,4). Both hypoxic conditions and chemical hydroxylase inhibitors (such as desferrioxamine and cobalt) inhibit HIF-1α degradation and lead to its stabilization. In addition, HIF-1α can be induced in an oxygen-independent manner by various cytokines through the PI3K-AKT-mTOR pathway (5-7).

HIF-1β is also known as AhR nuclear translocator (ARNT) due to its ability to partner with the aryl hydrocarbon receptor (AhR) to form a heterodimeric transcription factor complex (8). Together with AhR, HIF-1β plays an important role in xenobiotics metabolism (8). In addition, a chromosomal translocation leading to a TEL-ARNT fusion protein is associated with acute myeloblastic leukemia (9). Studies also found that ARNT/HIF-1β expression levels decrease significantly in pancreatic islets from patients with type 2 diabetes, suggesting that HIF-1β plays an important role in pancreatic β-cell function (10).

1. Sharp, F.R. and Bernaudin, M. (2004) Nat Rev Neurosci 5, 437-48.
2. Wang, G.L. et al. (1995) Proc Natl Acad Sci U S A 92, 5510-4.
3. Jaakkola, P. et al. (2001) Science 292, 468-72.
4. Maxwell, P.H. et al. (1999) Nature 399, 271-5.
5. Fukuda, R. et al. (2002) J Biol Chem 277, 38205-11.
6. Jiang, B.H. et al. (2001) Cell Growth Differ 12, 363-9.
7. Laughner, E. et al. (2001) Mol Cell Biol 21, 3995-4004.
8. Walisser, J.A. et al. (2004) Proc Natl Acad Sci U S A 101, 16677-82.
9. Salomon-Nguyen, F. et al. (2000) Proc Natl Acad Sci U S A 97, 6757-62.
10. Gunton, J.E. et al. (2005) Cell 122, 337-49.

注意事项：

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