Although p62/SQSTM1 was initially identified as an essential mediator of NFκB signaling, several recent studies have also highlighted its important role at the crossroad between the mTOR or MAPK signaling pathways and selective autophagy. The p62 structure containing important interaction domains attests to the ability of this protein to regulate and modulate the activation of these signaling pathways during tumor formation and propagation. The second very important function of this protein is to act as a molecular adaptor between the autophagic machinery and its substrates. Consequently, p62 is degraded following an increase in autophagic flux for which this protein currently serves as an indicator. However, the measurement of p62 expression strictly as a marker of autophagic flux is still controversial and can be misinterpreted mainly because this protein is subject to complex regulation at both the transcriptional and post-translational levels. Finally, because p62 is an autophagic substrate, it acts as a molecular link between cancer and autophagy by conferring a high level of selectivity through the degradation of important signaling molecules.
Keywords: Atg; MAPK; NFκB; NRF2; Paget’s disease; ROS; mTOR; oxidative stress; protein aggregates; ubiquitin.