Cold shock Y-box protein-1 participates in signaling circuits with auto-regulatory activities

Brandt, Sabine; Raffetseder, Ute; Djudjaj, Sonja; Schreiter, Anja; Kadereit, Bert; Michele, Melanie; Pabst, Melanie; Zhu, Cheng; Mertens, Peter R.

doi:10.1016/j.ejcb.2011.07.002

Cited by 29 publications

(21 citation statements)

References 81 publications

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“…Further studies would also focus on particular cell surface receptor(s) and downstream signal transduction pathway(s) associated with extracellular APE1 in the regulation of inflammation. Of note, several cell surface receptors (TLR2, TLR4 and receptor for advanced glycation end product; RAGE) for secretory HMGB1 [59] and Notch-3 for secretory YB-1 [60] have been reported to initiate signaling cascade leading to inflammatory regulation. As TLR4, TLR2 and RAGE receptors are also known to be involved in LPS-mediated stimulation of IL-6 production during inflammation, it is likely that secretory APE1 binds to RAGE receptors on monocytes or B-cells to induce IL-6 induction and secretion.…”

Section: Discussionmentioning

confidence: 99%

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

Nath

Roychoudhury

Kling

et al. 2017

Cellular Signalling

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The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear protein with roles in DNA base excision repair pathway as well as in regulation of transcription. Recently, the presence of extracellular plasma APE1 was reported in endotoxemic rats. However, the biological significance and the extracellular function of APE1 remain unclear. In this study, we found that monocytes secrete APE1 upon inflammatory challenges. Challenging the monocytic cells with extracellular APE1 resulted in the increased expression and secretion of the pro-inflammatory cytokine IL-6. Additionally, the extracellular APE1 treatment activated the transcription factor NF-κB, followed by its increased occupancy at the IL-6 promoter, resulting in the induction of IL-6 expression. APE1-induced IL-6 further served to elicit autocrine and paracrine cellular responses. Moreover, the extracellular IL-6 promoted the secretion of APE1, thus indicating a functional feedforward loop in this pathway. Furthermore, we show that APE1 is secreted through extracellular vesicles formation via endosomal sorting complex required for transport (ESCRT)-dependent pathway. Together, our study demonstrates a novel role of extracellular APE1 in IL-6-dependent cellular responses.

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Section: Discussionmentioning

confidence: 99%

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

Nath

Roychoudhury

Kling

et al. 2017

Cellular Signalling

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“…Cold shock proteins are evolutionarily conserved, and share a so-called cold shock domain [1,2]. In humans, three members of the protein family have been described, denoted DNA-binding protein A (DbpA) (also called zona occludens 1-associated nucleic acid binding protein (ZONAB) or cold shock domain A (CSDA)), DbpB (Y-box protein-1, YB-1), and DbpC (Contrin).…”

Section: Introductionmentioning

confidence: 99%

“…Transcription rates of proliferation-associated genes are upregulated by YB-1, e.g. DNA-polymerase-α, epidermal growth-factor receptor, platelet-derived growth factor, and matrix metalloproteinase-2 [1,2]. A pivotal role of YB-1 in cancerogenesis has been proposed by several groups, which has been substantiated by its interplay with c-Myc expression in multiple myeloma, as well as p53 function/signaling in malignant melanoma [4,5].…”

Section: Introductionmentioning

confidence: 99%

High prevalence of Y-box protein-1/p18 fragment in plasma of patients with malignancies of different origin

et al. 2014

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BackgroundExpression of the cold shock protein Y-box protein 1 (YB-1) is associated with deleterious outcome in various malignant diseases. Our group recently showed that the detection of an 18 kDa YB-1 fragment (YB-1/p18) in human plasma identifies patients with malignant diseases. We now tested the prevalence, clinical, and diagnostic value of YB-1/p18 detection in common tumors.MethodsA newly established monoclonal YB-1 antibody was used to detect YB-1/p18 by immunoblotting in plasma samples from 151 unselected tumor patients, alongside established tumor markers and various diagnostic measures, during evaluation for a cancerous disease and in follow-up studies after therapeutic interventions.ResultsCirculating YB-1/p18 was detected in 78% of patients having a tumor disease. YB-1/p18 positivity was highly prevalent in all examined malignancies, including lung cancer (32/37; 87%), breast cancer (7/10; 70%), cancer of unknown primary (CUP; 5/5, 100%) or hematological malignancies (42/62; 68%). Positivity for YB-1/p18 was independent of other routine laboratory parameters, tumor stage, or histology. In comparison to 13 established tumor markers (cancer antigens 15–3, 19–9, 72–4, and 125; carcinoembryonic antigen; cytokeratin fragments 21–1; neuron-specific enolase; alpha-fetoprotein; beta-2-microglobulin; squamous cell carcinoma antigen; thymidine kinase; tissue polypeptide antigen; pro-gastrin-releasing peptide), YB-1/p18 detection within serum samples was the most sensitive general parameter identifying malignant disorders. YB-1/p18 concentrations altered during therapeutic interventions, but did not predict prognosis.ConclusionsPlasma YB-1/p18 detection has a high specific prevalence in malignancies, thereby providing a novel tool for cancer screening independent of the tumor origin.

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“…YBPs were originally identified as proteins that bind to DNA, RNA, and other proteins (Sommerville and Ladomery, 1996; Matsumoto and Wolffe, 1998; Valadão et al, 2002; Evdokimova et al, 2006; Dong et al, 2009; Mihailovich et al, 2010; Eliseeva et al, 2011). Subsequent studies demonstrated that YB-1, a member of this family, is a major component of ribonucleoprotein particles (mRNPs), working on pre-mRNA splicing, mRNA stability, and translation (Mihailovich et al, 2010; Brandt et al, 2012). Thus, these proteins regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, induction of DNA repair, cellular proliferation, drug resistance, and stress responses to extracellular signals (Kohno et al, 2003; Mihailovich et al, 2010; Brandt et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1) potential as a vaccine candidate against schistosomiasis

et al. 2014

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Schistosomiasis is a neglected tropical disease, and after malaria, is the second most important tropical disease in public health. A vaccine that reduces parasitemia is desirable to achieve mass treatment with a low cost. Although potential antigens have been identified and tested in clinical trials, no effective vaccine against schistosomiasis is available. Y-box-binding proteins (YBPs) regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, DNA repair, cellular proliferation, drug resistance, and stress responses. The Schistosoma mansoni ortholog of the human YB-1, SMYB1, is expressed in all stages of the parasite life cycle. Although SMYB1 binds to DNA or RNA oligonucleotides, immunohistochemistry assays demonstrated that it is primarily localized in the cytoplasm of parasite cells. In addition, SMYB1 interacts with a protein involved in mRNA processing, suggesting that SMYB1 functions in the turnover, transport, and/or stabilization of RNA molecules during post-transcriptional gene regulation. Here we report the potential of SMYB1 as a vaccine candidate. We demonstrate that recombinant SMYB1 stimulates the production of high levels of specific IgG1 antibodies in a mouse model. The observed levels of specific IgG1 and IgG2a antibodies indicate an actual protection against cercariae challenge. Animals immunized with rSMYB1 exhibited a 26% reduction in adult worm burden and a 28% reduction in eggs retained in the liver. Although proteins from the worm tegument are considered optimal targets for vaccine development, this study demonstrates that unexposed cytoplasmic proteins can reduce the load of intestinal worms and the number of eggs retained in the liver.

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Cold shock Y-box protein-1 participates in signaling circuits with auto-regulatory activities

Cited by 29 publications

References 81 publications

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression

High prevalence of Y-box protein-1/p18 fragment in plasma of patients with malignancies of different origin

Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1) potential as a vaccine candidate against schistosomiasis

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