Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Aug;590(15):2375-97.
doi: 10.1002/1873-3468.12301. Epub 2016 Aug 6.

p62/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer

Koji Taniguchi  1   2   3 , Shinichiro Yamachika  1 , Feng He  1 , Michael Karin  1
Affiliations
Review

p62/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer

Koji Taniguchi et al. FEBS Lett. 2016 Aug.

Abstract

p62/SQSTM1 is a multifunctional signaling hub and autophagy adaptor with many binding partners, which allow it to activate mTORC1-dependent nutrient sensing, NF-κB-mediated inflammatory responses, and the NRF2-activated antioxidant defense. p62 recognizes polyubiquitin chains via its C-terminal domain and binds to LC3 via its LIR motif, thereby promoting the autophagic degradation of ubiquitinated cargos. p62 accumulates in many human liver diseases, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), where it is a component of Mallory-Denk bodies and intracellular hyaline bodies. Chronic p62 elevation contributes to HCC development by preventing oncogene-induced senescence and death of cancer-initiating cells and enhancing their proliferation. In this review, we discuss p62-mediated signaling pathways and their roles in liver pathophysiology, especially NASH and HCC.

Keywords: HCC; NASH; NF-κB; NRF2; autophagy; mTORC1; p62/SQSTM1.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Schematic representation of p62 structure and functional organization
Figure 2
Figure 2. (a-c) Pathways through which p62 promotes liver tumorigenesis (a, c) and regulates NASH (b)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Park I, et al. Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region. Proc Natl Acad Sci U S A. 1995;92(26):12338–42. - PMC - PubMed
    1. Okazaki M, et al. Cloning, expression profile, and genomic organization of the mouse STAP/A170 gene. Genomics. 1999;60(1):87–95. - PubMed
    1. Ishii T, et al. Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in response to oxidative stress. Biochem Biophys Res Commun. 1996;226(2):456–60. - PubMed
    1. Puls A, et al. Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein. Proc Natl Acad Sci U S A. 1997;94(12):6191–6. - PMC - PubMed
    1. Sanchez P, et al. Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62. Mol Cell Biol. 1998;18(5):3069–80. - PMC - PubMed

MeSH terms