ArticlePloS one2016
p62/Sequestosome-1 Is Indispensable for Maturation and Stabilization of Mallory-Denk Bodies.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Phospho-JNK agonists show promising effects for the treatment of hepatocellular carcinoma.iScience · 2026Article
- Cytochrome P450 as possible link between Mallory-Denk body formation in DDC-intoxicated mouse liver and human steatohepatitis.Virchows Archiv : an international journal of pathology · 2026Article
- A histomorphological analysis of the effects of Ghanaian alcoholic bitters and natural cocoa powder on the liver and kidney tissues in Sprague Dawley rats.Journal of molecular histology · 2026Article
- Targeting phase separation: a promising treatment option for hepatocellular carcinoma.Cell communication and signaling : CCS · 2025Review
- Liver CYP4A autophagic lysosomal degradation: A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site.Molecular pharmacology · 2025Article
- Role of SQSTM1/p62 in regulating Mallory-Denk body in alcohol-associated liver disease.eGastroenterology · 2025Article
- NAFLD (MASLD)/NASH (MASH): Does It Bother to Label at All? A Comprehensive Narrative Review.International journal of molecular sciences · 2024Review
- [Research Progress in the Role of Liquid-Liquid Phase Separation in Human Cancer].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.Acta pharmaceutica Sinica. B · 2024Article
- SQSTM1/p62 and Hepatic Mallory-Denk Body Formation in Alcohol-Associated Liver Disease.The American journal of pathology · 2023Review
- Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm.International journal of molecular sciences · 2022Review
- Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies.Nature structural & molecular biology · 2022Article
- Hepatocytic p62 suppresses ductular reaction and tumorigenesis in mouse livers with mTORC1 activation and defective autophagy.Journal of hepatology · 2022Article
- Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice.Acta pharmaceutica Sinica. B · 2021Article
- Autophagy in liver diseases: A review.Molecular aspects of medicine · 2021Review
- Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis.International journal of molecular sciences · 2021Article
- Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation.International journal of molecular sciences · 2021Article
- A Novel Mechanism for NF-κB-activation via IκB-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation.Molecular & cellular proteomics : MCP · 2020Article
- NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system.EMBO reports · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mallory-Denk bodies (MDBs) are hepatocytic protein aggregates found in steatohepatitis and several other chronic liver diseases as well as hepatocellular carcinoma. MDBs are mainly composed of phosphorylated keratins and stress protein p62/Sequestosome-1 (p62), which is a common component of cytoplasmic aggregates in a variety of protein aggregation diseases. In contrast to the well-established role of keratins, the role of p62 in MDB pathogenesis is still elusive. We have generated total and hepatocyte-specific p62 knockout mice, fed them with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to induce MDBs and allowed the mice to recover from DDC intoxication on a standard diet to investigate the role of p62 in MDB formation and elimination. In the absence of p62, smaller, granular and less distinct MDBs appeared, which failed to mature to larger and compact inclusions. Moreover, p62 deficiency impaired the binding of other proteins such as NBR1 and Hsp25 to MDBs and altered the cellular defense mechanism by downregulation of Nrf2 target genes. Upon recovery from DDC intoxication on a standard diet, there was an enhanced reduction of p62-deficient MDBs, which was accompanied by a pronounced decrease in ubiquitinated proteins. Our data provide strong evidence that keratin aggregation is the initial step in MDB formation in steatohepatitis-related mouse models. Interaction of p62 with keratin aggregates then leads to maturation i.e., enlargement and stabilization of the MDBs as well as recruitment of other MDB-associated proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.