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The Multifunctional Protein p62 and Its Mechanistic Roles in Cancers

[ Vol. 18 , Issue. ]

Author(s):

Shunbin Ning and Ling Wang*Pages 1-11 (11)

Abstract:


The multifunctional signaling hub p62 is well recognized as a ubiquitin sensor and a selective autophagy adaptor. As a ubiquitin sensor, p62 promotes NFκB activation by facilitating TRAF6 ubiquitination and aggregation. As a selective autophagy receptor, p62 links 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.

Keywords:

p62, autophagy, ubiquitination, ROS.

Affiliation:

Division of Infectious Diseases, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, Division of Infectious Diseases, Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614



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