Transglutaminase type 2-dependent crosslinking of IRF3 in dying melanoma cells

Occhigrossi, Luca; D’Eletto, Manuela; Vecchio, Alessio; Piacentini, Mauro; Rossin, Federica

doi:10.1038/s41420-022-01278-w

Cited by 4 publications

(1 citation statement)

References 28 publications

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“…In keeping with these findings, newly we showed that, upon doxorubicin treatment (Fig. 1), TG2 translocates into the nucleus and catalyzes the formation of covalent cross-linked IRF3 (Interferon regulatory factor 3) dimers, thereby limiting the production of IFNβ in dying melanoma cells [51].…”

Section: Potential Tg2/cbaf Interplay In Diseasesupporting

confidence: 80%

Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme

Rossin

Ciccosanti

D’Eletto

et al. 2023

Cell. Mol. Life Sci.

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One of the major mysteries in science is how it is possible to pack the cellular chromatin with a total length of over 1 m, into a small sphere with a diameter of 5 mm “the nucleus”, and even more difficult to envisage how to make it functional. Although we know that compaction is achieved through the histones, however, the DNA needs to be accessible to the transcription machinery and this is allowed thanks to a variety of very complex epigenetic mechanisms. Either DNA (methylation) or post-translational modifications of histone proteins (acetylation, methylation, ubiquitination and sumoylation) play a crucial role in chromatin remodelling and consequently on gene expression. Recently the serotonylation and dopaminylation of the histone 3, catalyzed by the Transglutaminase type 2 (TG2), has been reported. These novel post-translational modifications catalyzed by a predominantly cytoplasmic enzyme opens a new avenue for future investigations on the enzyme function itself and for the possibility that other biological amines, substrate of TG2, can influence the genome regulation under peculiar cellular conditions. In this review we analyzed the nuclear TG2’s biology by discussing both its post-translational modification of various transcription factors and the implications of its epigenetic new face. Finally, we will focus on the potential impact of these events in human diseases.

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Section: Potential Tg2/cbaf Interplay In Diseasesupporting

confidence: 80%

Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme

Rossin

Ciccosanti

D’Eletto

et al. 2023

Cell. Mol. Life Sci.

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cGAS-STING activation by nanodelivery of teniposide achieves colorectal cancer chemo-immunotherapy

Liao,

Chen,

shi

et al. 2024

European Polymer Journal

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Advances in the prerequisite and consequence of STING downstream signalosomes

Lu,

Li,

et al. 2024

Medical Review

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The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an evolving DNA-sensing mechanism involved in innate immunity and pathogen defense that has been optimized while remaining conserved. Aside from recognizing pathogens through conserved motifs, these receptors also detect aberrant or misplaced self-molecules as possible signs of perturbed homeostasis. Upon binding external or self-derived DNA, a mobile secondary messenger 2′3′-cyclic GMP-AMP (cGAMP) is produced by cGAS and in turn activates its adapter STING in the endoplasmic reticulum (ER). Resting-state or activated STING protein is finely restricted by multiple degradation machineries. The post-translational changes of the STING protein, along with the regulatory machinery of the secret routes, limit the onset, strength and sustention of STING signal. STING experiences a conformational shift and relocates with TBK1 from the ER to perinuclear vesicles containing transcription factors, provoking the transcription activity of IRF3/IFN-I and NF-κB pathways, as well as to initiate a number of cellular processes that have been shown to alter the immune landscape in cancer, such as autophagy, NLRP3 inflammasome, ER stress, and cell death. STING signal thus serves as a potent activator for immune mobilization yet also triggers immune-mediated pathology in tissues. Recent advances have established the vital role of STING in immune surveillance as well as tumorigenic process. This review provides an overview of the disparate outcomes of cancer attributed to the actions of pleiotropic and coordinated STING downstream signalosomes, along with the underlying mechanisms of STING function in pathologies, providing therapeutic implications for new approaches in hunt for the next generation of cancer immunotherapy base on STING.

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Transglutaminase type 2-dependent crosslinking of IRF3 in dying melanoma cells

Cited by 4 publications

References 28 publications

Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme

Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme

cGAS-STING activation by nanodelivery of teniposide achieves colorectal cancer chemo-immunotherapy

Advances in the prerequisite and consequence of STING downstream signalosomes

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