Gadd45β is critical for regulation of type I interferon signaling by facilitating G3BP-mediated stress granule formation

Chathuranga, W.A. Gayan; Nikapitiya, Chamilani; Kim, Jae-Hoon; Chathuranga, Kiramage; Weerawardhana, Asela; Dodantenna, Niranjan; Kim, Doo-Jin; Poo, Haryoung; Jung, Jae U.; Lee, Chul-Ho; Lee, Jong-Soo

doi:10.1016/j.celrep.2023.113358

Cited by 4 publications

(3 citation statements)

References 75 publications

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“…By the ninth day, the CD14+ monocyte‐derived macrophages (CD14 + MDM) were meticulously harvested, poised for subsequent experiments. mBMDM isolation was performed as described before 49 . In brief, the femurs and tibias were isolated from C57BL/6 J mice and flushed with medium.…”

Section: Methodsmentioning

confidence: 99%

“…48 mBMDM isolation was performed as described before. 49 In brief, the femurs and tibias were isolated from C57BL/6 J mice and flushed with medium. RBCs were removed by ACK lysis buffer (Gibco), cells were incubated with DMEM containing 10% FBS, 1% antibiotic-antimycotic, and mouse GM-CSF (10 ng/mL) for 6 days to be differentiated to BMDMs.…”

Section: Usp19-mediated Removal Of K11-linked Ubiquitin Chains Frommentioning

confidence: 99%

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SIAH1 modulates antiviral immune responses by targeting deubiquitinase USP19

Weerawardhana,

Herath,

Gayan Chathuranga

et al. 2024

Journal of Medical Virology

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Tight control of the type I interferon (IFN) signaling pathway is critical for maintaining host innate immune responses, and the ubiquitination and deubiquitination of signaling molecules are essential for signal transduction. Deubiquitinase ubiquitin‐specific protein 19 (USP19) is known to be involved in deubiquitinating Beclin1, TRAF3, and TRIF for downregulation of the type I IFN signaling. Here, we show that SIAH1, a cellular E3 ubiquitin ligase that is involved in multicellular pathway, is a potent positive regulator of virus‐mediated type I IFN signaling that maintains homeostasis within the antiviral immune response by targeting USP19. In the early stages of virus infection, stabilized SIAH1 directly interacts with the USP19 and simultaneously mediates K27‐linked ubiquitination of 489, 490, and 610 residues of USP19 for proteasomal degradation. Additionally, we found that USP19 specifically interacts with MAVS and deubiquitinates K63‐linked ubiquitinated MAVS for negative regulation of type I IFN signaling. Ultimately, we identified that SIAH1‐mediated degradation of USP19 reversed USP19‐mediated deubiquitination of MAVS, Beclin1, TRAF3, and TRIF, resulting in the activation of antiviral immune responses. Taken together, these findings provide new insights into the molecular mechanism of USP19 and SIAH1, and suggest a critical role of SIAH1 in antiviral immune response and homeostasis.

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Section: Methodsmentioning

confidence: 99%

Section: Usp19-mediated Removal Of K11-linked Ubiquitin Chains Frommentioning

confidence: 99%

SIAH1 modulates antiviral immune responses by targeting deubiquitinase USP19

Weerawardhana,

Herath,

Gayan Chathuranga

et al. 2024

Journal of Medical Virology

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“…19 Further, and similar to GADD45A, GADD45B and GADD45G play pivotal roles in innate immune responses and in a variety of inflammatory diseases. [20][21][22][23] Besides this, GADD45B can regulate angiogenesis, cell differentiation and migration, and oxidative stress, and it has recently been demonstrated that o modulates gluconeogenesis and lipid metabolism in the liver, [24][25][26][27] and neuroplasticity and neuroprotection in the nervous system. 28 In contrast, GADD45G has been reported to participate in primary sex determination and male fertility, 29 and the development of heart failure.…”

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confidence: 99%

GADD45A: With or without you

Palomer,

Salvador,

Griñán‐Ferré

et al. 2024

Medicinal Research Reviews

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The growth arrest and DNA damage inducible (GADD)45 family includes three small and ubiquitously distributed proteins (GADD45A, GADD45B, and GADD45G) that regulate numerous cellular processes associated with stress signaling and injury response. Here, we provide a comprehensive review of the current literature investigating GADD45A, the first discovered member of the family. We first depict how its levels are regulated by a myriad of genotoxic and non‐genotoxic stressors, and through the combined action of intricate transcriptional, posttranscriptional, and even, posttranslational mechanisms. GADD45A is a recognized tumor suppressor and, for this reason, we next summarize its role in cancer, as well as the different mechanisms by which it regulates cell cycle, DNA repair, and apoptosis. Beyond these most well‐known actions, GADD45A may also influence catabolic and anabolic pathways in the liver, adipose tissue and skeletal muscle, among others. Not surprisingly, GADD45A may trigger AMP‐activated protein kinase activity, a master regulator of metabolism, and is known to act as a transcriptional coregulator of numerous nuclear receptors. GADD45A has also been reported to display a cytoprotective role by regulating inflammation, fibrosis and oxidative stress in several organs and tissues, and is regarded an important contributor for the development of heart failure. Overall data point to that GADD45A may play an important role in metabolic, neurodegenerative and cardiovascular diseases, and also autoimmune‐related disorders. Thus, the potential mechanisms by which dysregulation of GADD45A activity may contribute to the progression of these diseases are also reviewed below.

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