p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targetin...

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Published inInternational journal of molecular sciences Vol. 21; no. 14; p. 5029
Main Authors Emanuele, Sonia, Lauricella, Marianna, D'Anneo, Antonella, Carlisi, Daniela, De Blasio, Anna, Di Liberto, Diana, Giuliano, Michela
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 16.07.2020
MDPI AG
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Summary:p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional protein, p62 falls into the category of those factors that can exert opposite roles in the cells. Chronic p62 accumulation was found in many types of tumors as well as in stress granules present in different forms of neurodegenerative diseases. However, the protein seems to have a Janus behaviour since it may also serve protective functions against tumorigenesis or neurodegeneration. This review describes the diversified roles of p62 through its multiple domains and interactors and specifically focuses on its and roles.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21145029