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Description
Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress, and autophagy. It was first identified as a protein that binds to the SH2 domain of p56Lck , and independently found to interact with PKCzeta. 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. Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-kappaB pathway. Protein aggregates formed by SQSTM1 can be degraded by the autophagosome. SQSTM1 binds autophagosomal membrane protein LC3/Atg8, bringing SQSTM1-containing protein aggregates to the autophagosome. 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. Thus, accumulation of SQSTM1 can lead to an increase in NRF2 activity.Synonyms: SQSTM1, A170, OSIL, PDB3, ZIP3, p60, p62, p62B