p38gamma regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock.
Activation of p38γ modulates the integrity of the complex formed by the human discs large protein (hDlg) with cytoskeletal proteins, which is important for cell adaptation to changes in environmental osmolarity. Here we report that, in response to hyperosmotic stress, p38γ also regulates formation of complexes between hDlg and the nuclear protein polypyrimidine tract-binding protein-associated-splicing factor (PSF). Following osmotic shock, p38γ in the cell nucleus increases its association with nuclear hDlg, thereby causing dissociation of hDlg-PSF complexes. Moreover, hDlg and PSF bind different RNAs; in response to osmotic shock, p38γ causes hDlg-PSF and hDlg-RNA dissociation independently of its kinase activity. These findings identify a novel nuclear complex and suggest a previously unreported function of p38γ, which is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment.
Sabio
Guadalupe
G
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, 28049 Madrid, Spain.
Cerezo-Guisado
María I
MI
Del Reino
Paloma
P
Iñesta-Vaquera
Francisco A
FA
Rousseau
Simon
S
Arthur
J Simon C
JS
Campbell
David G
DG
Centeno
Francisco
F
Cuenda
Ana
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D000074288:Discs Large Homolog 1 Protein; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D048291:Mitogen-Activated Protein Kinase 12 / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure / Q000502:physiology*; D000072670:PTB-Associated Splicing Factor; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D000072670:PTB-Associated Splicing Factor; D016601:RNA-Binding Proteins; D012313:RNA; D048291:Mitogen-Activated Protein Kinase 12