Open AccessThe Multifunctional Protein p62 and Its Mechanistic Roles in Cancers
Author(s) -
Shunbin Ning,
Ling Wang
Publication year - 2019
Publication title -
current cancer drug targets
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 91
eISSN - 1873-5576
pISSN - 1568-0096
DOI - 10.2174/1568009618666181016164920
Subject(s) - autophagy , ubiquitin , dna damage , immune system , biology , microbiology and biotechnology , lysosome , signalling , immunology , dna , gene , genetics , biochemistry , apoptosis , enzyme
The multifunctional signaling hub p62 is well recognized as a ubiquitin sensor and a selective autophagy receptor. As a ubiquitin sensor, p62 promotes NFκB activation by facilitating TRAF6 ubiquitination and aggregation. As a selective autophagy receptor, p62 sorts ubiquitinated substrates including p62 itself for lysosome-mediated degradation. p62 plays crucial roles in myriad cellular processes including DNA damage response, aging/senescence, infection and immunity, chronic inflammation, and cancerogenesis, dependent on or independent of autophagy. Targeting p62-mediated autophagy may represent a promising strategy for clinical interventions of different cancers. In this review, we summarize the transcriptional and post-translational regulation of p62, and its mechanistic roles in cancers, with the emphasis on its roles in regulation of DNA damage response and its connection to the cGAS-STING-mediated antitumor immune response, which is promising for cancer vaccine design.