p62 at the interface of autophagy, oxidative stress signaling, and cancer

Antioxid Redox Signal. 2012 Sep 1;17(5):786-93. doi: 10.1089/ars.2011.4394. Epub 2012 Jan 11.


Significance: Sequestosome 1 (p62/SQSTM1) is a multifunctional adapter protein implicated in selective autophagy, cell signaling pathways, and tumorigenesis.

Recent advances: Recent evidence has revealed that p62/SQSTM1 has a critical role in an oxidative stress response pathway by its direct interaction with the ubiquitin ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), which results in constitutive activation of the transcription factor NF-E2-related factor 2 (NRF2).

Critical issues: Both NRF2 and KEAP1 are frequently mutated in cancer. The findings just cited uncover a link between p62/SQSTM1, autophagy, and the KEAP1-NRF2 stress response pathway in tumorigenesis and shed light on the interplay between autophagy and cancer.

Future directions: Here, we review the mechanisms by which p62/SQSTM1 implements its multiple roles in the regulation of tumorigenesis with emphasis on the KEAP1-NRF2 stress response signaling pathway. Uncovering the molecular mechanisms of p62/SQSTM1 function in oxidative stress signaling might contribute to elucidating its role in tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Autophagy*
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oxidative Stress*
  • Sequestosome-1 Protein
  • Signal Transduction*


  • Adaptor Proteins, Signal Transducing
  • SQSTM1 protein, human
  • Sequestosome-1 Protein