Revision 4

#48768Store at -20C

1 Kit

(7 x 20 microliters)

Cell Signaling Technology

Orders: 877-616-CELL (2355) [email protected]

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3 Trask LaneDanversMassachusetts01923USA
For Research Use Only. Not for Use in Diagnostic Procedures.
Product Includes Product # Quantity Mol. Wt Isotype/Source
SQSTM1/p62 (D1Q5S) Rabbit mAb 39749 20 µl 62 kDa Rabbit IgG
Phospho-SQSTM1/p62 (Ser349) (E7M1A) Rabbit mAb 16177 20 µl 62 kDa Rabbit IgG
LC3A/B (D3U4C) XP® Rabbit mAb 12741 20 µl 14, 16 kDa Rabbit IgG
KEAP1 (D6B12) Rabbit mAb 8047 20 µl 60-64 kDa Rabbit IgG
NRF2 (D1Z9C) XP® Rabbit mAb 12721 20 µl 97-100 kDa Rabbit IgG
HO-1 (E3F4S) Rabbit mAb 43966 20 µl 28 kDa Rabbit IgG
NQO1 (D6H3A) Rabbit mAb 62262 20 µl 29 kDa Rabbit IgG
Anti-rabbit IgG, HRP-linked Antibody 7074 100 µl Goat 

Please visit for individual component applications, species cross-reactivity, dilutions, protocols, and additional product information.


The p62/KEAP1/NRF2 Pathway Antibody Sampler Kit provides an economical means of detecting the non-canonical mechanism of NRF2 activation involving autophagy. The kit includes enough antibodies to perform two western blot experiments with each primary antibody.


Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% sodium azide. Store at –20°C. Do not aliquot the antibodies.


The cap ’n’ collar (CNC), leucine zipper (bZIP) transcription factor NRF2 (also called nuclear factor erythroid 2-related factor 2 (NFE2L2)) is the master regulator of the cellular antioxidant response, regulating the expression of over 200 genes that contain antioxidant response elements (AREs) in their regulatory regions by heterodimerizing with small MAF proteins (1). While NRF2 is expressed in all cell types, its basal protein levels are usually kept low during homeostatic conditions, mainly by KEAP1 (Kelch-like ECH-associated protein 1). Under normal conditions, KEAP1 binds to and targets NRF2 for ubiquitination-dependent proteasomal degradation. Upon oxidative stress, KEAP1 is modified on some sensor cysteines, affecting its conformation and thus interfering its binding to NRF2, allowing newly synthesized NRF2 to accumulate and translocate to the nucleus to activate its target genes, including HO-1 (heme oxygenase 1) and NQO1 (NAD(P)H:quinone oxidoreductase 1) (2,3). Another mode of NRF2 regulation involves the autophagy adapter protein p62 (or sequestosome 1 [SQSTM1]) in a KEAP1-dependent but cysteine-independent manner, the so called non-canonical pathway. Autophagy is a tightly regulated cellular quality control system that removes damaged proteins or organelles. Autophagy can also be activated to degrade macromolecules to provide nutrients under cellular starvation stress. p62, especially upon phosphorylation at Ser349 (Ser351 in mouse p62), can compete with NRF2 for binding KEAP1 and, as a result, p62 sequesters KEAP1 into the autophagosome and prevents KEAP1-mediated NRF2 degradation. This process may also require autophagy protein LC3. In addition, studies also found that KEAP1 is a p62-regulated substrate for autophagy-mediated degradation, indicating that p62 also plays a role in controlling KEAP1 turnover (4,5). Dysregulation of autophagy results in prolonged NRF2 activation and this may contribute to many diseases, including cancer and neurodegenerative diseases (6-9).

  1. Zhu, M. and Fahl, W.E. (2001) Biochem Biophys Res Commun 289, 212-9.
  2. Bellezza, I. et al. (2018) Biochim Biophys Acta Mol Cell Res 1865, 721-33.
  3. Yamamoto, M. et al. (2018) Physiol Rev 98, 1169-203.
  4. Jiang, T. et al. (2015) Free Radic Biol Med 88, 199-204.
  5. Nezis, I.P. and Stenmark, H. (2012) Antioxid Redox Signal 17, 786-93.
  6. Rojo de la Vega, M. et al. (2018) Cancer Cell 34, 21-43.
  7. Sánchez-Martín, P. et al. (2019) FEBS J 286, 8-23.
  8. Shah, S.Z.A. et al. (2018) Front Mol Neurosci 11, 310.
  9. Ichimura, Y. and Komatsu, M. (2018) Front Oncol 8, 210.

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