Cell signalling is the complex network of connections between cells and inside the single cell. Protein trafficking is deeply involved in cell signalling. Different proteins are ordered in clusters of receptors of extracellular signals, transducers, sensors and biological response effectors. Together, they are arranged in molecular pathways that are required for the maintenance of cell homeostasis. Protein secretion is a relevant component of eukaryotic cell signalling. The prototype cold-shock Y-box binding protein 1 (YB- 1) is a multifunctional protein which regulates a variety of fundamental biological processes. Among them, cellular stress response and cell proliferation. Recently YB-1 has been found in human extracellular fluids and shown to be secreted by different cell types. My recent research activity was focused on YB-1 protein secretion to investigate on its role as a potential paracrine signal to elicit changes or responses in nearby cells, altering their behaviour. Low amounts of extracellular YB-1 are released by HEK293T cells in physiological condition. Interestingly, YB-1 secretion was enhanced following oxidative insults. In parallel, the assembly of YB-1 in stress granules (SGs), cytoplasmic foci where untranslated mRNAs are sorted or processed for re-initiation, degradation or packaging into mRNPs was verified. Purified recombinant human YB-1 (rYB-1) and enriched frac- tions of YB-1 from HEK293T cell culture medium (CCM-YB-1) were produced. Both forms of YB-1 protein have anti-proliferative activity on different recipient cell lines, including HaCaT cells. In particular, inhibition of human keratinocytes proliferation by extracellular YB-1 was associated to a G2/M cell cycle arrest, induction of p21WAF and reduction of 'Np63D protein level. The obtained results suggest that sustained release of full length YB-1 protein, by stress stimuli acts as paracrine/autocrine signal stimulating cell cycle arrest.
YB-1 protein is secreted as consequence of oxidative stress and induces G2/M phase block in receiving cells / Guarino, A. - In: RENDICONTO DELL'ACCADEMIA DELLE SCIENZE FISICHE E MATEMATICHE. - ISSN 0370-3568. - 86:(2020), pp. 7-23. [DOI 10.32092/1015]
YB-1 protein is secreted as consequence of oxidative stress and induces G2/M phase block in receiving cells
GUARINO A
2020
Abstract
Cell signalling is the complex network of connections between cells and inside the single cell. Protein trafficking is deeply involved in cell signalling. Different proteins are ordered in clusters of receptors of extracellular signals, transducers, sensors and biological response effectors. Together, they are arranged in molecular pathways that are required for the maintenance of cell homeostasis. Protein secretion is a relevant component of eukaryotic cell signalling. The prototype cold-shock Y-box binding protein 1 (YB- 1) is a multifunctional protein which regulates a variety of fundamental biological processes. Among them, cellular stress response and cell proliferation. Recently YB-1 has been found in human extracellular fluids and shown to be secreted by different cell types. My recent research activity was focused on YB-1 protein secretion to investigate on its role as a potential paracrine signal to elicit changes or responses in nearby cells, altering their behaviour. Low amounts of extracellular YB-1 are released by HEK293T cells in physiological condition. Interestingly, YB-1 secretion was enhanced following oxidative insults. In parallel, the assembly of YB-1 in stress granules (SGs), cytoplasmic foci where untranslated mRNAs are sorted or processed for re-initiation, degradation or packaging into mRNPs was verified. Purified recombinant human YB-1 (rYB-1) and enriched frac- tions of YB-1 from HEK293T cell culture medium (CCM-YB-1) were produced. Both forms of YB-1 protein have anti-proliferative activity on different recipient cell lines, including HaCaT cells. In particular, inhibition of human keratinocytes proliferation by extracellular YB-1 was associated to a G2/M cell cycle arrest, induction of p21WAF and reduction of 'Np63D protein level. The obtained results suggest that sustained release of full length YB-1 protein, by stress stimuli acts as paracrine/autocrine signal stimulating cell cycle arrest.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
