ArticleCell death & disease2015
Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Transglutaminase 2 regulates vimentin-dependent proteostasis during macrophage activation.Science advances · 2026Article
- Insights into programmed cell death from multiple imaging modalities.Journal of translational medicine · 2026Review
- OV16 Improves Radiation-Induced Intestinal Injury by Targeting Transglutaminase 2.Molecules (Basel, Switzerland) · 2026Article
- Transglutaminase 2 nuclear localization enhances glioblastoma radiation resistance.Discover oncology · 2025Article
- TGM2-Mediated Autophagy Contributes to the Radio-Resistance of Non-Small Cell Lung Cancer Stem-like Cells.Biomedicines · 2024Article
- Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid.Cell death & disease · 2023Article
- Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines.Cell death & disease · 2023Article
- Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme.Cellular and molecular life sciences : CMLS · 2023Review
- Nuclear Transglutaminase 2 interacts with topoisomerase II⍺ to promote DNA damage repair in lung cancer cells.Journal of experimental & clinical cancer research : CR · 2021Article
- Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis.International journal of molecular sciences · 2021Review
- Prevention of arachidonic acid-induced liver injury by controlling oxidative stress-mediated transglutaminase activation with garlic extracts.Experimental and therapeutic medicine · 2020Article
- Moonlighting Proteins Are Important Players in Cancer Immunology.Frontiers in immunology · 2020Review
- Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target.Molecular carcinogenesis · 2019Article
- Arachidonic acid suppresses hepatic cell growth through ROS-mediated activation of transglutaminase.FEBS open bio · 2018Article
- Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro.International journal of molecular sciences · 2018Article
- Review
- Transglutaminase-catalyzed incorporation of polyamines masks the DNA-binding region of the transcription factor Relish.The Journal of biological chemistry · 2017Article
- Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.World journal of gastroenterology · 2016Review
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear accumulation of transglutaminase 2 (TG2) is an important step in TG2-dependent cell death. However, the underlying molecular mechanisms for nuclear translocation of TG2 are still poorly understood. In this study, we demonstrated that acyclic retinoid (ACR) induced nuclear accumulation of TG2 in JHH-7 cells, a hepatocellular carcinoma (HCC) leading to their apoptosis. We further demonstrated molecular mechanism in nuclear-cytoplasmic trafficking of TG2 and an effect of ACR on it. We identified a novel 14-amino acid nuclear localization signal (NLS) (466)AEKEETGMAMRIRV(479) in the 'C' domain and a leucine-rich nuclear export signal (NES) (657)LHMGLHKL(664) in the 'D' domain that allowed TG2 to shuttle between the nuclear and cytosolic milieu. Increased nuclear import of GAPDH myc-HIS fused with the identified NLS was observed, confirming its nuclear import ability. Leptomycin B, an inhibitor of exportin-1 as well as point mutation of all leucine residues to glutamine residues in the NES of TG2 demolished its nuclear export. TG2 formed a trimeric complex with importin-α and importin-β independently from transamidase activity which strongly suggested the involvement of a NLS-based translocation of TG2 to the nucleus. ACR accelerated the formation of the trimeric complex and that may be at least in part responsible for enhanced nuclear localization of TG2 in HCC cells treated with ACR.
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