Cold shock Y-box binding protein-1 acetylation status in monocytes is associated with systemic inflammation and vascular damage

Ewert, Lara; Fischer, Anja; Brandt, Sabine; Scurt, Florian G; Philipsen, Lars; Müller, Andreas J.; Girndt, Matthias; Zenclussen, Ana Claudia; Lindquist, Jonathan A.; Gorny, Xenia; Mertens, Peter R.

doi:10.1016/j.atherosclerosis.2018.09.020

Cited by 21 publications

(23 citation statements)

References 47 publications

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“…Y-box binding protein-1 is related on an evolutionary level to HMGB1 and is also secreted under certain cellular stresses. This was first evident in monocytes stimulated with bacterial lipopolysaccharide through an active, non-classical pathway and appears to require the same two lysine residues (Lys301/304) that are the site of acetylation in hemodialysis patients (Frye et al, 2009; Ewert et al, 2018; Figures 3–5). Secreted YB-1 stimulated DNA synthesis, cell proliferation and migration of kidney cells (Frye et al, 2009).…”

Section: Yb-1: a Malignant Jack Of All Tradesmentioning

confidence: 99%

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Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma

Johnson

Schelch

Mehta

et al. 2019

Front. Cell Dev. Biol.

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Lung cancers and malignant pleural mesothelioma (MPM) have some of the worst 5-year survival rates of all cancer types, primarily due to a lack of effective treatment options for most patients. Targeted therapies have shown some promise in thoracic cancers, although efficacy is limited only to patients harboring specific mutations or target expression. Although a number of actionable mutations have now been identified, a large population of thoracic cancer patients have no therapeutic options outside of first-line chemotherapy. It is therefore crucial to identify alternative targets that might lead to the development of new ways of treating patients diagnosed with these diseases. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) could serve as one such target. Recent studies also link this protein to many inherent behaviors of thoracic cancer cells such as proliferation, invasion, metastasis and involvement in cancer stem-like cells. Here, we review the regulation of YB-1 at the transcriptional, translational, post-translational and sub-cellular levels in thoracic cancer and discuss its potential use as a biomarker and therapeutic target.

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Section: Yb-1: a Malignant Jack Of All Tradesmentioning

confidence: 99%

“…Here, YB-1 was acetylated at Lys64 (Figure 3). Lys301/304 of YB-1 can also be acetylated and the amount of acetylated YB-1 is significantly increased in monocytes of hemodialysis patients (Ewert et al, 2018).…”

Section: Yb-1: a Malignant Jack Of All Tradesmentioning

confidence: 99%

Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma

Johnson

Schelch

Mehta

et al. 2019

Front. Cell Dev. Biol.

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“…These cells are not only important for the induction of inflammation, but they also contribute to wound healing and the restoration of tissue homeostasis. Indeed, we and others have recently shown that YB-1 plays an essential role in each of these stages of disease [ 9 , 46 , 49 , 50 , 51 , 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

YB-1 Interferes with TNFα–TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNFα Signaling

Hessman

Hildebrandt

Shah

et al. 2020

IJMS

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Inflammation and an influx of macrophages are common elements in many diseases. Among pro-inflammatory cytokines, tumor necrosis factor α (TNFα) plays a central role by amplifying the cytokine network. Progranulin (PGRN) is a growth factor that binds to TNF receptors and interferes with TNFα-mediated signaling. Extracellular PGRN is processed into granulins by proteases released from immune cells. PGRN exerts anti-inflammatory effects, whereas granulins are pro-inflammatory. The factors coordinating these ambivalent functions remain unclear. In our study, we identify Y-box binding protein-1 (YB-1) as a candidate for this immune-modulating activity. Using a yeast-2-hybrid assay with YB-1 protein as bait, clones encoding for progranulin were selected using stringent criteria for strong interaction. We demonstrate that at physiological concentrations, YB-1 interferes with the binding of TNFα to its receptors in a dose-dependent manner using a flow cytometry-based binding assay. We show that YB-1 in combination with progranulin interferes with TNFα-mediated signaling, supporting the functionality with an NF-κB luciferase reporter assay. Together, we show that YB-1 displays immunomodulating functions by affecting the binding of TNFα to its receptors and influencing TNFα-mediated signaling via its interaction with progranulin.

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“…Recently, we showed that the acetylation status of Y-box binding protein-1 (YB-1; lysines 301/304) is enhanced in circulating monocytes of dialysis patients compare to healthy controls 8 . YB-1 is a ubiquitously expressed member of the cold shock protein family, which regulates transcription, RNA splicing, and translation via its nucleic acid binding activities.…”

Section: Introductionmentioning

confidence: 99%

Altered monocytic phenotypes are linked with systemic inflammation and may be linked to mortality in dialysis patients

Brandt

Ewert

Scurt

et al. 2019

Sci Rep

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The major causes for increased morbidity and mortality among chronic kidney disease patients are cardiovascular diseases and infection. A causal link between an activated immune system and aggravated atherosclerosis has been postulated that skews the system towards inflammatory responses. Previously, we demonstrated a positive association of pro-inflammatory cytokines with monocytic Y-box binding protein-1 (YB-1) expression and vessel wall infiltration in hemodialysis patients. Here, we question whether the responsiveness and cytokine repertoire of monocytes is altered by pre-activation and how this correlates with survival. EDTA whole blood from hemodialysis patients (n = 45) and healthy controls (n = 34) was collected and leukocytes challenged with LPS. The distribution of monocyte subsets, YB-1acetyl content, and serum cytokine levels were determined. Compared to controls, dialysis patients have fewer classical (Mo1) and more intermediate (Mo2) and non-classical (Mo3) monocytes. In response to LPS, the Mo2 subset significantly increases (p < 0.001) in control subjects, but not in hemodialysis patients; increased CD86 expression indicates a positive response to LPS. Based on the changes within Mo2, subjects could be classified as responders or non-responders: 60% non-responders were seen in the dialysis cohort versus only 35% among healthy controls. YB-1 acetylation is higher in dialysis patients, independent of LPS stimulation. In this small cohort with 72 months follow-up period intracellular YB-1acetyl levels, IL-6, uPAR, and IP10 correlated with excess mortality in the dialysis cohort. Changes in YB-1 acetylation and serum cytokines may, at a given time point, possibly predict the long-term outcome and thus provide a legacy effect in hemodialysis patients.

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Cold shock Y-box binding protein-1 acetylation status in monocytes is associated with systemic inflammation and vascular damage

Cited by 21 publications

References 47 publications

Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma

Why Be One Protein When You Can Affect Many? The Multiple Roles of YB-1 in Lung Cancer and Mesothelioma

YB-1 Interferes with TNFα–TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNFα Signaling

Altered monocytic phenotypes are linked with systemic inflammation and may be linked to mortality in dialysis patients

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