ArticleThe Journal of biological chemistry2010
Opposing effects of two tissue transglutaminase protein isoforms in neuroblastoma cell differentiation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Canonical and Truncated Transglutaminase-2 Drive TGF-β1 Autocrine Loop to Induce Fibrosis in Graves' Orbitopathy.Investigative ophthalmology & visual science · 2025Article
- Distinct conformational states enable transglutaminase 2 to promote cancer cell survival versus cell death.Communications biology · 2024Article
- Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors.Cells · 2024Review
- Dysregulation of Transglutaminase type 2 through GATA3 defines aggressiveness and Doxorubicin sensitivity in breast cancer.International journal of biological sciences · 2022Article
- Structures of Human Transglutaminase 2: Finding Clues for Interference in Cross-linking Mediated Activity.International journal of molecular sciences · 2020Review
- Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status.International journal of molecular sciences · 2020Article
- The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression.Medical sciences (Basel, Switzerland) · 2019Review
- Differential Expression of Tissue Transglutaminase Splice Variants in Peripheral Blood Mononuclear Cells of Primary Progressive Multiple Sclerosis Patients.Medical sciences (Basel, Switzerland) · 2018Article
- Opening up about Tissue Transglutaminase: When Conformation Matters More than Enzymatic Activity.Med one · 2018Article
- Interplay between transglutaminases and heparan sulphate in progressive renal scarring.Scientific reports · 2016Article
- Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death.Cell death & disease · 2016Review
- Article
- Histone deacetylase 5 blocks neuroblastoma cell differentiation by interacting with N-Myc.Oncogene · 2014Article
- The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1.Oncotarget · 2014Article
- Crystallization and preliminary X-ray crystallographic studies of transglutaminase 2 in complex with Ca2+.Acta crystallographica. Section F, Structural biology communications · 2014Article
- Transglutaminase regulation of cell function.Physiological reviews · 2014Review
- Induction and translocation of tissue transglutaminase isoforms increased phosphorylation in retinoic acid treated erythroleukemia cells.The protein journal · 2013Article
- The histone deacetylase SIRT2 stabilizes Myc oncoproteins.Cell death and differentiation · 2013Article
- Transglutaminase 6: a protein associated with central nervous system development and motor function.Amino acids · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have demonstrated previously that the Myc oncoprotein blocks cancer cell differentiation by forming a novel transcriptional repressor complex with histone deacetylase and inhibiting gene transcription of tissue transglutaminase (TG2). Moreover, induction of TG2 gene transcription and transamidase activity is essential for the differentiating effects of retinoids in cancer cells. Here, we show that two structurally distinct TG2 protein isoforms, the full-length (TG2-L) and the short form (TG2-S), exert opposing effects on cell differentiation. Repression of TG2-L with small interfering RNA, which did not affect TG2-S expression, induced dramatic neuritic differentiation in neuroblastoma cells. In contrast, overexpression of TG2-S or a GTP-binding-deficient mutant of TG2-L (R580A), both of which lack the GTP-binding Arg-580 residue, induced neuroblastoma cell differentiation, which was blocked by an inhibitor of transamidase activity. Whereas N-Myc repressed and retinoid activated both TG2 isoforms, repression of TG2-L, but not simultaneous repression of TG2-L and TG2-S, enhanced neuroblastoma cell differentiation due to N-Myc small interfering RNA or retinoid. Moreover, suppression of vasoactive intestinal peptide (VIP) expression alone induced neuroblastoma cell differentiation, and VIP was up-regulated by TG2-L, but not TG2-S. Taken together, our data indicate that TG2-L and TG2-S exert opposite effects on cell differentiation due to differences in GTP binding and modulation of VIP gene transcription. Our findings highlight the potential importance of repressing the GTP binding activity of TG2-L or activating the transamidase activity of TG2-L or TG2-S for the treatment of neuroblastoma, and possibly also other Myc-induced malignancies, and for enhancing retinoid anticancer effects.
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