Phospho-SQSTM1/p62 (Thr269/Ser272) Antibody

• 产品编号：CST-13121S      品牌：CST       原厂货号：13121S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho- SQSTM1/p62 (Thr269/Ser272) Antibody可特异性识别内源性的苏氨酸（269位点）和丝氨酸（272位点）磷酸化的SQSTM1蛋白。该抗体与双磷酸化或单磷酸化的SQSTM1都可反应。在一些细胞系中，在75kDa处能够检测到背景条带。该多克隆抗体是通过用合成肽免疫动物制备的，该合成肽的序列与人QSTM1/p62 蛋白的Thr269/Ser272周围的残基相一致。抗体通过蛋白A以及多肽亲和色谱法纯化。

Sequestosome 1 (SQSTM1, p62) 是一种涉及细胞信号、氧化应激和自噬的泛素结合蛋白(1-4)。初次被鉴定为能够结合p56Lck的SH2域的一种蛋白(5)，并且可以独立地与PKCζ相互作用(6,7)。随后研究发现，其能够与泛素相互作用，为多种信号蛋白提供支架，通过蛋白酶体或溶酶体触发蛋白的降解(8)。SQSTM1与TRAF6的相互作用，导致K63连接的TRAF6的多泛素化作用，以及随后的NF-κB通路的激活(9)。蛋白通过SQSTM1形成聚合物，能够被自噬小体降解(4,10,11)。SQSTM1能够结合自噬小体膜蛋白LC3/Atg8，将含有SQSTM-1的蛋白聚合物运输到自噬小体处(12)。在自噬过程中，溶酶体降解自噬小体从而导致SQSTM1水平的降低，相反，自噬抑制剂可以稳定SQSTM1的水平。研究证明了，SQSTM1和氧化应激之间的关系。SQSTM1可以与KEAP1相互作用，KEAP1是NRF2的细胞质抑制剂，一个关键的细胞转录因子(3)。因此，SQSTM1的累积能够导致NRF2的活化。

1. Kirkin, V. et al. (2009) Mol Cell 34, 259-69.
2. Seibenhener, M.L. et al. (2007) FEBS Lett 581, 175-9.
3. Komatsu, M. et al. (2010) Nat Cell Biol 12, 213-23.
4. Bjørkøy, G. et al. (2006) Autophagy 2, 138-9.
5. Joung, I. et al. (1996) Proc Natl Acad Sci USA 93, 5991-5.
6. Sanchez, P. et al. (1998) Mol Cell Biol 18, 3069-80.
7. Puls, A. et al. (1997) Proc Natl Acad Sci USA 94, 6191-6.
8. Vadlamudi, R.K. et al. (1996) J Biol Chem 271, 20235-7.
9. Wooten, M.W. et al. (2005) J Biol Chem 280, 35625-9.
10. Bjørkøy, G. et al. (2005) J Cell Biol 171, 603-14.
11. Komatsu, M. et al. (2007) Cell 131, 1149-63.
12. Pankiv, S. et al. (2007) J Biol Chem 282, 24131-45.
13. Linares, J.F. et al. (2011) Mol Cell Biol 31, 105-17.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Monkey

Specificity / Sensitivity

Phospho-SQSTM1/p62 (Thr269/Ser272) Antibody recognizes endogenous levels of SQSTM1 protein only when phosphorylated at Thr269 and Ser272. This antibody may react with either dually or singly phosphorylated SQSTM1/p62. A background band is detected at 75 kDa in some cell lines.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Thr269/Ser272 of human SQSTM1/p62 protein. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress and autophagy (1-4). It was first identified as a protein that binds to the SH2 domain of p56Lck (5) and independently found to interact with PKCζ (6,7). SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome (8). Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway (9). Protein aggregates formed by SQSTM1 can be degraded by the autophagosome (4,10,11). SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome (12). Lysosomal degradation of autophagosomes leads to a decrease in SQSTM1 levels during autophagy; conversely, autophagy inhibitors stabilize SQSTM1 levels. Studies have demonstrated a link between SQSTM1 and oxidative stress. SQSTM1 interacts with KEAP1, which is a cytoplasmic inhibitor of NRF2, a key transcription factor involved in cellular responses to oxidative stress (3). Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.

1. Kirkin, V. et al. (2009) Mol Cell 34, 259-69.
2. Seibenhener, M.L. et al. (2007) FEBS Lett 581, 175-9.
3. Komatsu, M. et al. (2010) Nat Cell Biol 12, 213-23.
4. Bjørkøy, G. et al. (2006) Autophagy 2, 138-9.
5. Joung, I. et al. (1996) Proc Natl Acad Sci USA 93, 5991-5.
6. Sanchez, P. et al. (1998) Mol Cell Biol 18, 3069-80.
7. Puls, A. et al. (1997) Proc Natl Acad Sci USA 94, 6191-6.
8. Vadlamudi, R.K. et al. (1996) J Biol Chem 271, 20235-7.
9. Wooten, M.W. et al. (2005) J Biol Chem 280, 35625-9.
10. Bjørkøy, G. et al. (2005) J Cell Biol 171, 603-14.
11. Komatsu, M. et al. (2007) Cell 131, 1149-63.
12. Pankiv, S. et al. (2007) J Biol Chem 282, 24131-45.
13. Linares, J.F. et al. (2011) Mol Cell Biol 31, 105-17.

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.