PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation

Fontana, Rosa; Guidone, Daniela; Sangermano, Felicia; Calabrò, Viola; Pollice, Alessandra; Mantia, Girolama La; Vivo, Maria

doi:10.1038/s41598-018-25496-4

Cited by 13 publications

(20 citation statements)

References 45 publications

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“…Every 24 h cells were gently rinsed with 1× PBS, trypsinized and counted. The count was confirmed by Scepter 2.0 analysis (Millipore, Burlington, MI, USA) as previously described [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Oxidative Stress Causes Enhanced Secretion of YB-1 Protein that Restrains Proliferation of Receiving Cells

Guarino

Troiano

Pizzo

et al. 2018

Genes

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The prototype cold-shock Y-box binding protein 1 (YB-1) is a multifunctional protein that regulates a variety of fundamental biological processes including cell proliferation and migration, DNA damage, matrix protein synthesis and chemotaxis. The plethora of functions assigned to YB-1 is strictly dependent on its subcellular localization. In resting cells, YB-1 localizes to cytoplasm where it is a component of messenger ribonucleoprotein particles. Under stress conditions, YB-1 contributes to the formation of stress granules (SGs), cytoplasmic foci where untranslated messenger RNAs (mRNAs) are sorted or processed for reinitiation, degradation, or packaging into ribonucleoprotein particles (mRNPs). Following DNA damage, YB-1 translocates to the nucleus and participates in DNA repair thereby enhancing cell survival. Recent data show that YB-1 can also be secreted and YB-1-derived polypeptides are found in plasma of patients with sepsis and malignancies. Here we show that in response to oxidative insults, YB-1 assembly in SGs is associated with an enhancement of YB-1 protein secretion. An enriched fraction of extracellular YB-1 (exYB-1) significantly inhibited proliferation of receiving cells and such inhibition was associated to a G2/M cell cycle arrest, induction of p21WAF and reduction of ΔNp63α protein level. All together, these data show that acute oxidative stress causes sustained release of YB-1 as a paracrine/autocrine signal that stimulate cell cycle arrest.

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“…Every 24 h cells were gently rinsed with 1× PBS, trypsinized and counted. The count was confirmed by Scepter 2.0 analysis (Millipore, Burlington, MI, USA) as previously described [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Oxidative Stress Causes Enhanced Secretion of YB-1 Protein that Restrains Proliferation of Receiving Cells

Guarino

Troiano

Pizzo

et al. 2018

Genes

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“…Total protein was extracted with cell extraction buffer using the following formulation: 100 mMTris pH 7.4, 2 mM Na3VO4, 100 mM NaCl, 1% NP40, 1 mM EDTA, 1 mMNaF, 0.5% deoxycholate, 20 mM Na4P2O7, 1 mM PMSF, and 1X Protease Inhibitor Cocktail (Sigma) as previously described (Di Martino et al, 2016;Fontana et al, 2018). Protein concentrations were determined using the Bio-Rad protein assay kit according to the manufacturer's instructions.…”

Section: Western Blot Analysismentioning

confidence: 99%

Retinoic Acid Induces Embryonic Stem Cells (ESCs) Transition to 2 Cell-Like State Through a Coordinated Expression of Dux and Duxbl1

Tagliaferri

Mazzone

Noviello

et al. 2020

Front. Cell Dev. Biol.

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Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) of the blastocyst. In serum/LIF culture condition, they show variable expression of pluripotency genes that mark cell fluctuation between pluripotency and differentiation metastate. The ESCs subpopulation marked by zygotic genome activation gene (ZGA) signature, including Zscan4, retains a wider differentiation potency than epiblast-derived ESCs. We have recently shown that retinoic acid (RA) significantly enhances Zscan4 cell population. However, it remains unexplored how RA initiates the ESCs to 2-cell like reprogramming. Here we found that RA is decisive for ESCs to 2C-like cell transition, and reconstructed the gene network surrounding Zscan4. We revealed that RA regulates 2C-like population co-activating Dux and Duxbl1. We provided novel evidence that RA dependent ESCs to 2C-like cell transition is regulated by Dux, and antagonized by Duxbl1. Our suggested mechanism could shed light on the role of RA on ESC reprogramming.

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“…The observation that ARF, similar to ATG proteins, localizes to FAs during cell spreading opens the way to the possibility that its function relies on the activation of autophagy at specific sites within the cell. Moreover, the regulation of ARF by protein kinase C (PKC) suggests that, since its tumor suppressor ability can switch off [ 17 , 61 ], its function in autophagy can be regulated by post-translational modifications as well.…”

Section: Regulation Of Autophagymentioning

confidence: 99%

“…As ARF localization to nucleoli has been correlated with its ability to block cell proliferation and ribosomal RNA processing [ 93 ], it would be interesting to analyze ARF’s role in nucleolar FAK functions and recruitment. Moreover, given the role of ARF phosphorylation in its cellular localization, it would be worth evaluating its role in this process [ 17 , 61 ]. ARF activity in the cytoplasm appears to be timely regulated by a PKC-mediated mechanism.…”

Section: Arf–fak Cross-talkmentioning

confidence: 99%

“…Moreover, in thyroid tumors, a strong delocalization of the protein in the cytoplasm has been observed and correlated with a negative prognosis [ 16 ]. Recently, we showed that during cell spreading, p14ARF protein levels increase in the cytoplasm thanks to the activation of protein kinase C (PKC) [ 17 ]. ARF phosphorylation, by inducing ARF accumulation in the cytoplasm, stabilizes focal adhesion kinase (FAK) and allows cell spreading.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of p14ARF and Focal Adhesion Kinase-Mediated Autophagy in Cancer

Fontana

Vivo

2018

Cancers

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It has been widely shown that the focal adhesion kinase (FAK) is involved in nearly every aspect of cancer, from invasion to metastasis to epithelial–mesenchymal transition and maintenance of cancer stem cells. FAK has been shown to interact with p14ARF (alternative reading frame)—a well-established tumor suppressor—and functions in the negative regulation of cancer through both p53-dependent and -independent pathways. Interestingly, both FAK and ARF (human and mouse counterpart) proteins, as well as p53, are involved in autophagy—a process of “self-digestion”—whose main function is the recycling of cellular components and quality control of proteins and organelles. In the last years, an unexpected role of p14ARF in the survival of cancer cells has been underlined in different cellular contexts, suggesting a novel pro-oncogenic function of this protein. In this review, the mechanisms whereby ARF and FAK control autophagy are presented, as well as the role of autophagy in cell migration and spreading. Integrated investigation of these cell functions is extremely important to understand the mechanism of the basis of cell transformation and migration and thus cancer development.

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PKC Dependent p14ARF Phosphorylation on Threonine 8 Drives Cell Proliferation

Cited by 13 publications

References 45 publications

Oxidative Stress Causes Enhanced Secretion of YB-1 Protein that Restrains Proliferation of Receiving Cells

Oxidative Stress Causes Enhanced Secretion of YB-1 Protein that Restrains Proliferation of Receiving Cells

Retinoic Acid Induces Embryonic Stem Cells (ESCs) Transition to 2 Cell-Like State Through a Coordinated Expression of Dux and Duxbl1

Dynamics of p14ARF and Focal Adhesion Kinase-Mediated Autophagy in Cancer

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