ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Keratin 8 phosphorylation regulates its transamidation and hepatocyte Mallory-Denk body formation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Role of SQSTM1/p62 in regulating Mallory-Denk body in alcohol-associated liver disease.eGastroenterology · 2025Article
- SQSTM1/p62 and Hepatic Mallory-Denk Body Formation in Alcohol-Associated Liver Disease.The American journal of pathology · 2023Review
- Deacetylation via SIRT2 prevents keratin-mutation-associated injury and keratin aggregation.JCI insight · 2023Article
- From Strain Stiffening to Softening-Rheological Characterization of Keratins 8 and 18 Networks Crosslinked via Electron Irradiation.Polymers · 2022Article
- Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis.International journal of molecular sciences · 2021Article
- Revealing the Roles of Keratin 8/18-Associated Signaling Proteins Involved in the Development of Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- Correlation of hepatitis C virus-mediated endoplasmic reticulum stress with autophagic flux impairment and hepatocarcinogenesis.Medical molecular morphology · 2021Article
- Liver disease-associated keratin 8 and 18 mutations modulate keratin acetylation and methylation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Intermediate filament proteins of digestive organs: physiology and pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Post-translational modifications of intermediate filament proteins: mechanisms and functions.Nature reviews. Molecular cell biology · 2014Review
- A conserved rod domain phosphotyrosine that is targeted by the phosphatase PTP1B promotes keratin 8 protein insolubility and filament organization.The Journal of biological chemistry · 2013Article
- Lamin aggregation is an early sensor of porphyria-induced liver injury.Journal of cell science · 2013Article
- Glucose and SIRT2 reciprocally mediate the regulation of keratin 8 by lysine acetylation.The Journal of cell biology · 2013Article
- Keratin 8 variants are infrequent in patients with alcohol-related liver cirrhosis and do not associate with development of hepatocellular carcinoma.BMC gastroenterology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
Mallory-Denk bodies (MDBs) are hepatocyte inclusions that are associated with poor liver disease prognosis. The intermediate filament protein keratin 8 (K8) and its cross-linking by transglutaminase-2 (TG2) are essential for MDB formation. K8 hyperphosphorylation occurs in association with liver injury and MDB formation, but the link between keratin phosphorylation and MDB formation is unknown. We used a mutational approach to identify K8 Q70 as a residue that is important for K8 cross-linking to itself and other liver proteins. K8 cross-linking is markedly enhanced on treating cells with a phosphatase inhibitor and decreases dramatically on K8 S74A or Q70N mutation in the presence of phosphatase inhibition. K8 Q70 cross-linking, in the context of synthetic peptides or intact proteins transfected into cells, is promoted by phosphorylation at K8 S74 or by an S74D substitution and is inhibited by S74A mutation. Transgenic mice that express K8 S74A or a K8 G62C liver disease variant that inhibits K8 S74 phosphorylation have a markedly reduced ability to form MDBs. Our findings support a model in which the stress-triggered phosphorylation of K8 S74 induces K8 cross-linking by TG2, leading to MDB formation. These findings may extend to neuropathies and myopathies that are characterized by intermediate filament-containing inclusions.
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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.