Abstract:
Sequestosome1 (p62/SQSTM 1) is a multidomain protein that interacts with the autophagy
machinery as a key adaptor of target cargo. It interacts with phagophores through the LC3-interacting
(LIR) domain and with the ubiquitinated protein aggregates through the ubiquitin-associated
domain (UBA) domain. It sequesters the target cargo into inclusion bodies by its PB1 domain.
This protein is further the central hub that interacts with several key signaling proteins. Emerging
evidence implicates p62 in the induction of multiple cellular oncogenic transformations. Indeed,
p62 upregulation and/or reduced degradation have been implicated in tumor formation, cancer
promotion as well as in resistance to therapy. It has been established that the process of autophagy
regulates the levels of p62. Autophagy-dependent apoptotic activity of p62 is recently being reported.
It is evident that p62 plays a critical role in both autophagy and apoptosis. Therefore in this review
we discuss the role of p62 in autophagy, apoptosis and cancer through its different domains and
outline the importance of modulating cellular levels of p62 in cancer therapeutics.
