Calcineurin-mediated YB-1 Dephosphorylation Regulates CCL5 Expression during Monocyte Differentiation

Abstract

Background: Transcription factor YB-1 constitutes a key regulator in immune cell homeostasis. It has been demonstrated to be involved in monocyte/macrophage differentiation. However, the underlying mechanisms are poorly understood. Results: Protein phosphatase calcineurin (CN) regulates YB-1 activities on the CCL5 promoter during macrophage differentiation. Conclusion: Dephosphorylation of YB-1 by CN is crucial to counteract the overwhelming pro-inflammatory propensities of YB-1. Significance: Overshooting inflammation may be counteracted by dephosphorylation of YB-1.

Alternatively activated macrophages in the pathogenesis of chronic kidney allograft injury

“…Furthermore, a variety of studies have described the role of macrophages in tissue remodeling and fibrosis in organ diseases including kidney injury and allograft injury [8,9,14]. It has also been proposed that epithelial to mesenchymal transition might play a crucial role in renal fibrosis via macrophage-derived factors such as TGF-β and matrix metalloproteinase-9 [15,16] Although the mechanisms that promote macrophage accumulation in chronic kidney diseases (including CAI) have not been elucidated, there are various factors that can induce macrophage accumulation, including renal vascular injury caused by ischemia, calcineurin inhibitor (CNI) toxicity, and infections; these could induce chemokine expression for macrophages from injured vascular endothelial cells and tubular epithelial cells [17,18].…”

Y-Box Binding Proteins in mRNP Assembly, Translation, and Stability Control

“…Of note, upon transcription inhibition, not only the cytoplasmic mRNA content but also YB-1 modifications play a key role in the YB-1 nuclear import [211]. The best-studied YB-1 modification is its phosphorylation at Ser102 by Akt or RSK [75,161,162], which promotes YB-1 nuclear accumulation [159][160][161] by an unknown mechanism. YB-1 undergoes some other modifications (Table 1) that can also modulate its RNA-binding activity and/or nuclear-cytoplasmic transport.…”

The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial Cell Proliferation, Apoptosis, and Angiogenesis

“…The ancient and highly conserved CSD of YB1 has an intrinsically disordered spatial structure, allowing interactions with various molecules, including transcription factors, gene promoters, and mRNAs (Lyabin et al, 2014). This property allows YB1 to play a broad role in various cellular processes, including transcriptional regulation (Alidousty et al, 2014), pro-mRNA splicing, mRNA stability, mRNA translation (Lyabin et al, 2013), DNA repair (Lyabin et al, 2014), and drug resistance (Shiota et al, 2014).…”