p38γ regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock

Sabio, Guadalupe; Cerezo-Guisado, María Isabel; Reino, Paloma del; Iñesta-Vaquera, Francisco; Rousseau, Stéphane; Arthur, J. Simon C.; Campbell, David G.; Centeno, Francisco; Cuenda, Ana

doi:10.1242/jcs.066514

Cited by 22 publications

(27 citation statements)

References 32 publications

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“…One possibility is modulation of the affinity of PSF for its targets. For example, interaction of the scaffold protein hDlg with its kinase p38γ decreases hDlg/PSF association . Conversely, the addition of poly(ADP‐ribose) (PAR) to proteins (PARylation) increases the binding affinity of NONO, and perhaps PSF, through interaction of PAR with RRM1 .…”

Section: Regulation Of Psfmentioning

confidence: 99%

“…For example, interaction of the scaffold protein hDlg with its kinase p38 decreases hDlg/PSF association. 107 Conversely, the addition of poly(ADP-ribose) (PAR) to proteins (PARylation) increases the binding affinity of NONO, and perhaps PSF, through interaction of PAR with RRM1. 108 PARylation of histones is often a mark for sites of DNA damage and has been linked to recruitment of PSF and p54nrb/NONO for DNA repair.…”

Section: Psf-co-associated Proteinsmentioning

confidence: 99%

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PSF: nuclear busy‐body or nuclear facilitator?

et al. 2015

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PTB‐associated splicing factor (PSF) is an abundant and essential nucleic acid‐binding protein that participates in a wide range of gene regulatory processes and cellular response pathways. At the protein level, PSF consists of multiple domains, many of which remain poorly characterized. Although grouped in a family with the proteins p54nrb/NONO and PSPC1 based on sequence homology, PSF contains additional protein sequence not included in other family members. Consistently, PSF has also been implicated in functions not ascribed to p54nrb/NONO or PSPC1. Here, we provide a review of the cellular activities in which PSF has been implicated and what is known regarding the mechanisms by which PSF functions in each case. We propose that the complex domain arrangement of PSF allows for its diversity of function and integration of activities. Finally, we discuss recent evidence that individual activities of PSF can be regulated independently from one another through the activity of domain‐specific co‐factors. WIREs RNA 2015, 6:351–367. doi: 10.1002/wrna.1280For further resources related to this article, please visit the WIREs website.Conflict of interest: The authors declare no conflict of interest.

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Section: Regulation Of Psfmentioning

confidence: 99%

Section: Psf-co-associated Proteinsmentioning

confidence: 99%

PSF: nuclear busy‐body or nuclear facilitator?

et al. 2015

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“…Previous studies showed that p38␥ is both cytoplasmic and nuclear, whereas its phosphorylated form is predominantly localized in the nucleus (33)(34)(35). Because phosphorylated p38␥ protein is up-regulated in K-Ras mutant cells (15), we examined whether K-Ras mutation triggers p38␥ nuclear translocation, thus increasing its interaction with c-Jun.…”

Section: P38␥ Stimulates Egfr Transcription Through C-jun-mediated Bimentioning

confidence: 99%

The K-Ras effector p38γ MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulating EGFR transcription and EGFR dephosphorylation

Yin

Lepp

et al. 2017

Journal of Biological Chemistry

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Mutations in K-Ras and epidermal growth factor receptor (EGFR) are mutually exclusive, but it is not known how K-Ras activation inactivates EGFR, leading to resistance of cancer cells to anti-EGFR therapy. Here, we report that the K-Ras effector p38γ MAPK confers intrinsic resistance to small molecular tyrosine kinase inhibitors (TKIs) by concurrently stimulating gene trancription and protein dephosphorylation. We found that p38γ increases transcription by c-Jun-mediated promoter binding and stimulates EGFR dephosphorylation via activation of protein-tyrosine phosphatase H1 (PTPH1). Silencing the p38γ/c-Jun/PTPH1 signaling network increased sensitivities to TKIs in K-Ras mutant cells in which EGFR knockdown inhibited growth. Similar results were obtained with the p38γ-specific pharmacological inhibitor pirfenidone. These results indicate that in K-Ras mutant cancers, EGFR activity is regulated by the p38γ/c-Jun/PTPH1 signaling network, whose disruption may be a novel strategy to restore the sensitivity to TKIs.

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“…In yeast, it has been reported that, in response to osmotic or heat stress, Hog1 and Mpk1, respectively, phosphorylate components of the nuclear pore complex to increase the export efficiency of stress-responsive mRNAs [72,73]. Similarly, in mammals, both p38 and ERK pathways regulate RNA-binding proteins such as eIF4E or hDl1 that facilitate mRNA export [74,75]. In the event of stress, the export of the newly transcribed mRNAs is prioritized to maximize the transcriptional response.…”

Section: Mrna Exportmentioning

confidence: 99%

Shaping the Transcriptional Landscape through MAPK Signaling

Nadal-Ribelles¹,

Solé²,

Martínez-Cebrián³

et al. 2019

Gene Expression and Control

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A change in the transcriptional landscape is an equilibrium-breaking event important for many biological processes. Mitogen-activated protein kinase (MAPK) signaling pathways are dedicated to sensing extracellular cues and are highly conserved across eukaryotes. Modulation of gene expression in response to the extracellular environment is one of the main mechanisms by which MAPK regulates proteome homeostasis to orchestrate adaptive responses that determine cell fate. A massive body of knowledge generated from population and single-cell analyses has led to an understanding of how MAPK pathways operate. MAPKs have thus emerged as fundamental transcriptome regulators that function through a multilayered control of gene expression, a process often deregulated in disease, which therefore provides an attractive target for therapeutic strategies. Here, we summarize the current understanding of the mechanisms underlying MAPK-mediated gene expression in organisms ranging from yeast to mammals.

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p38γ regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock

Cited by 22 publications

References 32 publications

PSF: nuclear busy‐body or nuclear facilitator?

PSF: nuclear busy‐body or nuclear facilitator?

The K-Ras effector p38γ MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulating EGFR transcription and EGFR dephosphorylation

Shaping the Transcriptional Landscape through MAPK Signaling

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