RT Journal Article
T1 C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: Involvement in cell death
A1 Gutiérrez Uzquiza, Álvaro
A1 Arechederra, María
A1 Molina, Isabel
A1 Baños, Rocío
A1 Maia, Vera
A1 Benito De Las Heras, Manuel R.
A1 Guerrero, Carmen
A1 Porras Gallo, María Almudena
AB We present here evidences supporting a negative regulation of p38α 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 p38α 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 p38α activation, which plays an anti-apoptotic role under these conditions. Moreover, the C3G target, Rap-1, plays an opposite role, also through regulation of p38α 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 p38α 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 p38α MAPK in MEFs, while Rap-1 is a positive regulator, but both, through the regulation of p38α activity, can promote cell survival or cell death depending on the stimuli.
PB Elsevier
SN 0898-6568
YR 2010
FD 2010-03
LK https://hdl.handle.net/20.500.14352/93512
UL https://hdl.handle.net/20.500.14352/93512
LA eng
NO Gutiérrez-Uzquiza Á, Arechederra M, Molina I, Baños R, Maia V, Benito M, et al. C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: Involvement in cell death. Cellular Signalling 2010;22:533–42. https://doi.org/10.1016/j.cellsig.2009.11.008.
NO Instituto de Salud Carlos III
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad de Madrid
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 19 jul 2024