Prothymosin α and a prothymosin α-derived peptide enhance TH1-type immune responses against defined HER-2/neu epitopes

Ioannou, Kyriaki; Derhovanessian, Evelyna; Tsakiri, Eleni N.; Samara, Pinelopi; Kalbacher, Hubert; Voelter, Wolfgang; Trougakos, Ioannis P.; Pawelec, Graham; Tsitsilonis, Ourania E.

doi:10.1186/1471-2172-14-43

Cited by 22 publications

(24 citation statements)

References 66 publications

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“…PTMA is a highly acidic protein, that is, expressed both in the nucleus and cytosol of astrocytes (Halder & Ueda, 2012). Similar to C3, PTMA is also involved in propagation of inflammatory signals via its C-terminal domain that stimulates pro-inflammatory responses and cytokine expression through activation of toll like receptor 4 (Gusella, Teixeira, Aberg, Uversky, & Mosoian, 2016;Ioannou et al, 2013;Mosoian et al, 2010). LOX is an amine oxidase that converts primary amines into aldehydes generating hydrogen peroxide and ammonium as byproducts (Williamson & Kagan, 1987).…”

Section: Adev-il-10mentioning

confidence: 99%

Stimulus‐dependent modifications in astrocyte‐derived extracellular vesicle cargo regulate neuronal excitability

Chaudhuri

Dasgheyb

DeVine

et al. 2019

Glia

100

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Extracellular vesicles have now emerged as key players in cell‐to‐cell communication. This is particularly important in the central nervous system, where glia–neuron cross‐talk helps maintain normal neuronal function. Astrocyte‐derived extracellular vesicles (ADEVs) secreted constitutively promote neurite outgrowth and neuronal survival. However, extracellular stimuli can alter the cargo and downstream functions of ADEVs. For example, ADEVs secreted in response to inflammation contain cargo microRNAs and proteins that reduce neurite outgrowth, neuronal firing, and promote neuronal apoptosis. We performed a comprehensive quantitative proteomic analysis to enumerate the proteomic cargo of ADEVs secreted in response to multiple stimuli. Rat primary astrocytes were stimulated with a trophic stimulus (adenosine triphosphate, ATP), an inflammatory stimulus (IL‐1β) or an anti‐inflammatory stimulus (IL10) and extracellular vesicles secreted within a 2 hr time frame were collected using sequential ultracentrifugation method. ADEVs secreted constitutively without exposure to any stimulus were used a control. A tandem mass tag‐based proteomic platform was used to identify and quantify proteins in the ADEVs. Ingenuity pathway analysis was performed to predict the downstream signaling events regulated by ADEVs. We found that in response to ATP or IL10, ADEVs contain a set of proteins that are involved in increasing neurite outgrowth, dendritic branching, regulation of synaptic transmission, and promoting neuronal survival. In contrast, ADEVs secreted in response to IL‐1β contain proteins that regulate peripheral immune response and immune cell trafficking to the central nervous system.

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Section: Adev-il-10mentioning

confidence: 99%

Stimulus‐dependent modifications in astrocyte‐derived extracellular vesicle cargo regulate neuronal excitability

Chaudhuri

Dasgheyb

DeVine

et al. 2019

Glia

100

View full text Add to dashboard Cite

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“…tumor-specific T-lymphocyte response, interleukin-2 receptor expression or T[H]1-type immune responses). [10][11][12][13][14][15] Recently, two new PTMA variants (iso b and pseudogene 7) lack of nuclear localization signal (NLS) were isolated and identified from CD8 + T cells and cervicovaginal lavage with potent anti-HIV-1 activity, which were suggested to be innate immune mediators involved in immune surveillance. [16][17][18][19][20] PTMA can induce the import of Kelch-like ECHassociated protein 1 (Keap1) into the nucleus to inhibit nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response through Nrf2 degradation.…”

Section: Introductionmentioning

confidence: 99%

Prothymosin‐α enhances phosphatase and tensin homolog expression and binds with tripartite motif‐containing protein 21 to regulate Kelch‐like ECH‐associated protein 1/nuclear factor erythroid 2‐related factor 2 signaling in human bladder cancer

et al. 2019

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Prothymosin‐α ( PTMA ) is a small, acidic protein that is usually transported into the nucleus and involves many cellular and immunological functions. Previous studies demonstrated that aberrant location of PTMA expression exists in human bladder cancer, but the role of PTMA protein expression remains elusive. In this study, we created ectopic nuclear or cytoplasmic PTMA expression in human bladder cancer cells by infecting lentiviruses carrying wild type or deleted nuclear localization signal of the PTMA gene. The in vivo tumorigenesis assay showed PTMA protein with deleted nuclear localization signal promotes J82 xenograft tumor growth in mice and shortens their survival more so than the wild type. Chromatin immunoprecipitation showed that wild‐type PTMA protein binds to the PTEN promoter and enhances phosphatase and tensin homolog ( PTEN ) expression. Through immunoblot proteomics and in vivo ubiquitination studies, PTMA protein can bind with tripartite motif‐containing protein 21 ( TRIM 21) and block its ubiquitination. Also, TRIM 21 can downregulate both forms of PTMA protein. In human bladder tumors, loss of nuclear PTMA expression was an unfavorable prognostic indicator for shorter disease‐free survival (hazard ratio, 1.54; P = 0.009). Our data support that nuclear PTMA protein serves as a tumor suppressor in bladder cancer through upregulating PTEN and orchestrating TRIM 21 for the regulation of Nrf2 signaling.

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“…Prothymosin alpha (ProTα), a nuclear protein, is implicated in multiple functions including cell survival, proliferation and immunogenicity (Jiang et al, 2003;Mosoian, 2011;Ueda et al, 2012;Cannavo et al, 2013;Emmanouilidou et al, 2013;Ioannou et al, 2013;Chang et al, 2014;Lin et al, 2015). We previously identified ProTα as an anti-necrotic factor in the conditioned medium of a serum-free primary culture of cortical neurons (Ueda et al, 2007;Ueda, 2009).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective impact of prothymosin alpha-derived hexapeptide against retinal ischemia–reperfusion

et al. 2016

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Prothymosin alpha (ProTα) has robustness roles against brain and retinal ischemia or serum-starvation stress. In the ProTα sequence, the active core 30-amino acid peptide/P30 (a.a.49-78) is necessary for the original neuroprotective actions against ischemia. Moreover, the 9-amino acid peptide sequence/P9 (a.a.52-60) in P30 still shows neuroprotective activity against brain and retinal ischemia, though P9 is less potent than P30. As the previous structure-activity relationship study for ProTα may not be enough, the possibility still exists that any sequence smaller than P9 retains potent neuroprotective activity. When different P9- and P30-related peptides were intravitreally injected 24h after retinal ischemia in mice, the 6-amino acid peptide/P6 (NEVDEE, a.a.51-56) showed potent protective effects against ischemia-induced retinal functional deficits, which are equipotent to the level of P30 peptide in electroretinography (ERG) and histological damage in Hematoxylin and Eosin (HE) staining. Further studies using ERG and HE staining suggested that intravitreal or intravenous (i.v.) injection with modified P6 peptide/P6Q (NEVDQE) potently inhibited retinal ischemia-induced functional and histological damage. In an immunohistochemical analysis, the ischemia-induced loss of retinal ganglion, bipolar, amacrine and photoreceptor cells were inhibited by a systemic administration with P6Q peptide 24h after the ischemic stress. In addition, systemic post-treatment with P6Q peptide significantly inhibited retinal ischemia-induced microglia and astrocyte activation in terms of increased ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) intensity, respectively, as well as their morphological changes, increased number and migration. Thus, this study demonstrates the therapeutic significance of modified P6 peptide P6Q (NEVDQE) derived from 6-amino acid peptide (P6) in ProTα against ischemic damage.

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Prothymosin α and a prothymosin α-derived peptide enhance TH1-type immune responses against defined HER-2/neu epitopes

Cited by 22 publications

References 66 publications

Stimulus‐dependent modifications in astrocyte‐derived extracellular vesicle cargo regulate neuronal excitability

Stimulus‐dependent modifications in astrocyte‐derived extracellular vesicle cargo regulate neuronal excitability

Prothymosin‐α enhances phosphatase and tensin homolog expression and binds with tripartite motif‐containing protein 21 to regulate Kelch‐like ECH‐associated protein 1/nuclear factor erythroid 2‐related factor 2 signaling in human bladder cancer

Neuroprotective impact of prothymosin alpha-derived hexapeptide against retinal ischemia–reperfusion

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