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 PKCζ. 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-κB pathway. It may play a role in titin/TTN downstream signaling in muscle cells and regulate signaling cascades through ubiquitination. P62 may be involved in cell differentiation, apoptosis, immune response and regulation of K+ channels.
