C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: involvement in cell death

Cellular Signalling
Alvaro Gutiérrez-UzquizaAlmudena Porras

Abstract

We present here evidences supporting a negative regulation of p38alpha MAPK activity by C3G in MEFs triggered by stress, which can mediate cell death or survival depending on the stimuli. Upon serum deprivation, C3G induces survival through inhibition of p38alpha activation, which mediates apoptosis. In contrast, in response to H2O2, C3G behaves as a pro-apoptotic molecule, as its knock-down or knock-out enhances survival through up-regulation of p38alpha activation, which plays an anti-apoptotic role under these conditions. Moreover, the C3G target, Rap-1, plays an opposite role, also through regulation of p38alpha MAPK activity. Our data also suggest that changes in the protein levels of some members of the Bcl-2 family could account for the regulation of cell death by C3G and/or Rap-1 through p38alpha MAPK. Bim/Bcl-xL ratio appears to be important in the regulation of cell survival, both upon serum deprivation and in response to H2O2. In addition, the increase in BNIP-3 levels induced by C3G knock-down in wt cells treated with H2O2 might play a role preventing cell death. Therefore, we can conclude that C3G is a negative regulator of p38alpha MAPK in MEFs, while Rap-1 is a positive regulator, but both, through the regulation...Continue Reading

References

Jun 6, 2000·Trends in Biochemical Sciences·A R Nebreda, A Porras
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May 8, 2007·Biochimica Et Biophysica Acta·Ana Cuenda, Simon Rousseau
May 17, 2007·Apoptosis : an International Journal on Programmed Cell Death·Paloma BragadoAlmudena Porras
May 10, 2008·Apoptosis : an International Journal on Programmed Cell Death·Beibei Cai, Zhengui Xia
Feb 21, 2009·Cell Death and Differentiation·J Zhang, P A Ney

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Citations

Dec 6, 2011·The Journal of Biological Chemistry·Álvaro Gutiérrez-UzquizaAlmudena Porras
Sep 8, 2015·International Journal of Molecular Sciences·María García-ÁlvaroBlanca Herrera
Mar 4, 2011·Bioscience Reports·Vegesna RadhaKotagiri Sasikumar
Apr 8, 2020·Signal Transduction and Targeted Therapy·Sara Gutiérrez-HerreroCarmen Guerrero
Nov 4, 2020·Scientific Reports·Divya SriramVegesna Radha
Apr 17, 2020·Signal Transduction and Targeted Therapy·Sara Gutiérrez-HerreroCarmen Guerrero

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