The interplay between TGF‐β‐stimulated TSC22 domain family proteins regulates cell‐cycle dynamics in medulloblastoma cells

Dragotto, Jessica; Canterini, Sonia; Porto, Paola Del; Bevilacqua, Arturo; Fiorenza, Maria Teresa

doi:10.1002/jcp.28468

Cited by 15 publications

(13 citation statements)

References 56 publications

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“…GILZ, ubiquitously expressed, is primarily regulated by glucocorticoid receptor (GR) signaling to transduce glucocorticoid (GC) effects (31)(32)(33)(34). GILZ is known to regulate cell apoptosis, proliferation and differentiation, and to modulate host immunity and inflammation (35)(36)(37)(38)(39). More evidence suggesting the crucial role of GILZ in LPS resistance comes from mice receiving recombinant cell-permeable GILZ protein.…”

Section: Introductionmentioning

confidence: 99%

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

Jennings

Nelson

et al. 2020

Front. Immunol.

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Alcohol differentially affects human health, depending on the pattern of exposure. Moderate intake provides beneficial mood modulation and an anti-inflammatory effect, while excessive consumption leads to immunosuppression and various alcohol use disorders. The mechanism underlying this bi-phasic action mode of alcohol has not been clearly defined. Our previous publication demonstrated that ethanol, in the absence of glucocorticoids (GCs), induces expression of Glucocorticoid-Induced Leucine Zipper (GILZ), a key molecule that transduces GC anti-inflammatory effect through a non-canonical activation of glucocorticoid receptor (1). Here we report that similar short-chain alcohols, such as ethanol, propanol and isopropanol, share the same property of upregulating GILZ gene expression, and blunt cell inflammatory response in vitro. When mice were exposed to these alcohols, GILZ gene expression in immune cells was augmented in a dose-dependent manner. Monocytes and neutrophils were most affected. The short-chain alcohols suppressed host inflammatory response to lipopolysaccharide (LPS) and significantly reduced LPS-induced mortality. Intriguingly, propanol and isopropanol displayed more potent protection than ethanol at the same dose. Inhibition of ethanol metabolism enhanced the ethanol protective effect, suggesting that it is ethanol, not its derivatives or metabolites, that induces immune suppression. Taken together, short-chain alcohols per se upregulate GILZ gene expression and provide immune protection against LPS toxicity, suggesting a potential measure to counter LPS septic shock in a resource limited situation.

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Section: Introductionmentioning

confidence: 99%

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

Jennings

Nelson

et al. 2020

Front. Immunol.

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“…The TSC22D family includes leucine zipper proteins that are differentially expressed and involved in the regulation of multiple biological processes (13). TSC22D isoform heterodimers regulate cell cycle entry and exit (14).…”

Section: Introductionmentioning

confidence: 99%

Implicating the Role of GILZ in Glucocorticoid Modulation of T-Cell Activation

et al. 2019

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Glucocorticoid-induced leucine zipper (GILZ) is a protein with multiple biological roles that is upregulated by glucocorticoids (GCs) in both immune and non-immune cells. Importantly, GCs are immunosuppressive primarily due to their regulation of cell signaling pathways that are crucial for immune system activity. GILZ, which is transcriptionally induced by the glucocorticoid receptor (GR), mediates part of these immunosuppressive, and anti-inflammatory effects, thereby controlling immune cell proliferation, survival, and differentiation. The primary immune cells targeted by the immunosuppressive activity of GCs are T cells. Importantly, the effects of GCs on T cells are partially mediated by GILZ. In fact, GILZ regulates T-cell activation, and differentiation by binding and inhibiting factors essential for T-cell function. For example, GILZ associates with nuclear factor-κB (NF-κB), c-Fos, and c-Jun and inhibits NF-κB-, and AP-1-dependent transcription. GILZ also binds Raf and Ras, inhibits activation of Ras/Raf downstream targets, including mitogen-activated protein kinase 1 (MAPK1). In addition GILZ inhibits forkhead box O3 (FoxO3) without physical interaction. GILZ also promotes the activity of regulatory T cells (Tregs) by activating transforming growth factor-β (TGF-β) signaling. Ultimately, these actions inhibit T-cell activation and modulate the differentiation of T helper (Th)-1, Th-2, Th-17 cells, thereby mediating the immunosuppressive effects of GCs on T cells. In this mini-review, we discuss how GILZ mediates GC activity on T cells, focusing mainly on the therapeutic potential of this protein as a more targeted anti-inflammatory/immunosuppressive GC therapy.

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“…In the TSC-22 family, the function of TSC-22 (TSC22D1-2) has been widely studied [16,[18][19][20]24,[28][29][30][31][32][33][34][35][36][37]. The expression of TSC-22 (TSC22D1-2) is increased by various growth factors and hormones (TGF-β, FSH, TNF-α, EGF, FGF2) or cellular stress (activation of the RAS/MAP kinase pathway), and the TSC-22 (TSC22D1-2) protein induces differentiation, inhibits proliferation, and induces apoptosis in various cells [8][9][10][11][12][13][14]35,38,39] (Figure 1B). In addition, TSC22(86) (TSC22D1-3), which is upregulated by DNA damage, induces cellular senescence, such as senescence-associated heterochromatin foci (SAHF) formation and the senescence-associated secretary phenotype (SASP) [20].…”

Section: Introductionmentioning

confidence: 99%

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

Kamimura

Uchida

Kanno

et al. 2021

IJMS

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TSC-22 (TGF-β stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

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The interplay between TGF‐β‐stimulated TSC22 domain family proteins regulates cell‐cycle dynamics in medulloblastoma cells

Cited by 15 publications

References 56 publications

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response

Implicating the Role of GILZ in Glucocorticoid Modulation of T-Cell Activation

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

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