Prothymosin alpha-receptor associates with lipid rafts in PHA-stimulated lymphocytes

Salgado, Francisco; Piñeiro, Antonio; Canda-Sánchez, Ana; Lojo, Juan; Nogueira, Marco Aurélio

doi:10.1080/09687860500063506

Cited by 12 publications

(20 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The most probable candidate would be a cell surface receptor. Indeed, the presence of a cell surface ProTα receptor has been reported in lymphoid cells (Pineiro et al, 2001; Salgado et al, 2005), and we confirmed this in cortical neurons by using ProTα–Alexa 488 (Fig. S5, available at http://www.jcb.org/cgi/content/full/jcb.200608022/DC1).…”

Section: Discussionsupporting

confidence: 84%

Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

Ueda

Fujita

Yoshida

et al. 2007

The Journal of Cell Biology

104

View full text Add to dashboard Cite

We initially identified a nuclear protein, prothymosin-α1 (ProTα), as a key protein inhibiting necrosis by subjecting conditioned media from serum-free cultures of cortical neurons to a few chromatography steps. ProTα inhibited necrosis of cultured neurons by preventing rapid loss of cellular adenosine triphosphate levels by reversing the decreased membrane localization of glucose transporters but caused apoptosis through up-regulation of proapoptotic Bcl2-family proteins. The apoptosis caused by ProTα was further inhibited by growth factors, including brain-derived neurotrophic factor. The ProTα-induced cell death mode switch from necrosis to apoptosis was also reproduced in experimental ischemia-reperfusion culture experiments, although the apoptosis level was markedly reduced, possibly because of the presence of growth factors in the reperfused serum. Knock down of PKCβII expression prevented this cell death mode switch. Collectively, these results suggest that ProTα is an extracellular signal protein that acts as a cell death mode switch and could be a promising candidate for preventing brain strokes with the help of known apoptosis inhibitors.

show abstract

Section: Discussionsupporting

confidence: 84%

Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

Ueda

Fujita

Yoshida

et al. 2007

The Journal of Cell Biology

104

View full text Add to dashboard Cite

show abstract

“…Two binding sites, of low and high aYnity, were identiWed, both of which were speciWc for proT , but not T 1. In a subsequent study, Piñeiro and colleagues revealed three binding "partners" for proT in the membrane of lymphoblasts, which formed a cap-like structure on one of the cell's poles and associated with lipid rafts [37,38]. Most recently, proT was suggested to ligate toll-like receptor (TLR)-4, signal through the TRIF-dependent pathway and induce interferon (IFN)-production [39].…”

Section: The Dual-intracellular and Extracellular-role Of Protmentioning

confidence: 96%

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Ioannou

Samara

Livaniou

et al. 2012

Cancer Immunol Immunother

View full text Add to dashboard Cite

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as "thymic hormones," are produced by this gland. Although the majority of them have not been proven to be thymus-specific, thymic peptides comprise an effective group of regulators, mediating important immune functions. Thymosin fraction five (TFV) was the first thymic extract shown to stimulate lymphocyte proliferation and differentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin α (proTα) and thymosin α1 (Tα1) showed that they are of clinical significance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeficiencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their effect are yet not fully elucidated, proTα and Tα1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proTα, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of Tα1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proTα into the clinical setting.

show abstract

“…Furthermore, a number of cell surface binding proteins have been identified as candidate receptors for extracellular ProT␣. Regarding the anti-HIV effect of ProT␣ that we described here for macrophages, it remains to be determined if this is mediated via uptake of the exogenously added protein or via the induction of a signaling pathway (42).…”

Section: Discussionmentioning

confidence: 99%

Novel Function of Prothymosin Alpha as a Potent Inhibitor of Human Immunodeficiency Virus Type 1 Gene Expression in Primary Macrophages

Mosoian

Teixeira

High

et al. 2006

J Virol

View full text Add to dashboard Cite

CD8؉ T lymphocytes control human immunodeficiency virus type 1 (HIV-1) infection by a cytotoxic major histocompatibility complex-restricted pathway as well as by secretion of noncytotoxic soluble inhibitory factors. Several components of CD8؉ cell supernatants have been identified that contribute to the latter activity. In this study we report that prothymosin alpha (ProT␣), a protein found in the cell culture medium of the herpesvirus saimiri-transformed CD8 ؉ T-cell line, K#1 50K, has potent HIV-1-inhibitory activity. Depletion of native ProT␣ from an HIV-1-inhibitory fraction of CD8 ؉ cell supernatants removes the inhibitory activity, supporting its role in inhibition via soluble mediators. ProT␣ is an abundant, acidic peptide that has been reported to be localized in the nucleus and associated with cell proliferation and activation of transcription. In this report we demonstrate that ProT␣ suppresses HIV-1 replication, its activity is target cell specific, and inhibition occurs following viral integration. Native and recombinant ProT␣ protein potently inhibit HIV-1 long terminal repeat (LTR)-driven gene expression in macrophages. Furthermore studies using different promoters in lentiviral vectors (cytomegalovirus and phosphoglycerate kinase) revealed that suppression of viral replication by ProT␣ is not HIV LTR specific.

show abstract

Prothymosin alpha-receptor associates with lipid rafts in PHA-stimulated lymphocytes

Cited by 12 publications

References 57 publications

Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

Identification of prothymosin-α1, the necrosis–apoptosis switch molecule in cortical neuronal cultures

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

Novel Function of Prothymosin Alpha as a Potent Inhibitor of Human Immunodeficiency Virus Type 1 Gene Expression in Primary Macrophages

Contact Info

Product

Resources

About