SQSTM1/p62 (D1D9E3) Rabbit mAb (Alexa Fluor? 488 Conjugate)

• 产品编号：CST-8833S      品牌：CST       原厂货号：8833S
• 产品分类：抗体 > 一抗 > 染料标记抗体
• 应用分类：

描述：

SQSTM1/p62 (D1D9E3) Rabbit mAb (Alexa Fluor® 488 Conjugate) 兔单抗能够识别内源性的SQSTM1/p62总蛋白。该单克隆抗体通过合成肽免疫动物制备，这种合成肽的序列与人源的SQSTM1/p62蛋白羧基末端周围的残基相一致。该Cell Signaling Technology antibody 抗体与 Alexa Fluor® 488 荧光染料相结合，通过流式细胞术以及免疫荧光在人类细胞上进行了内部验证。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.

原厂资料：

Specificity / Sensitivity

SQSTM1/p62 (D1D9E3) Rabbit mAb (Alexa Fluor® 488 Conjugate) recognizes endogenous levels of total SQSTM1/p62 protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human SQSTM1/p62 protein.

Description

This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in human cells.

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.

注意事项：

Storage: Supplied in PBS (pH 7.2), less than 0.1% sodium
azide and 2 mg/ml BSA. Store at 4°C. Do not aliquot the anti-
body. Protect from light. Do not freeze.