Flowchart: Preparation: Ras
 


                 

       

Text Box: P53Text Box: P73                                        

                                                 

                                                                                     

 


Liver disease

Text Box: Ras                                                  

 

 

Text Box: Mapk                                                                                                         

                                  

 

                                                                                                                                                                                                                                                                  

 

 

Cell Death Differ. 2006 Apr 28; [Epub ahead of print]

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p73 cooperates with Ras in the activation of MAP kinase signaling cascade.

Fernandez-Garcia B, Vaque JP, Herreros-Villanueva M, Marques-Garcia F, Castrillo F, Fernandez-Medarde A, Leon J, Marin MC.

1Instituto de Biomedicina, Universidad de Leon, Campus de Vegazana, Leon 24071, Spain.

The p73 gene is capable of inducing cell cycle arrest, apoptosis, senescence, differentiation and to cooperate with oncogenic Ras in cellular transformation. Ras can be considered as a branch point in signal transduction, where diverse extracellular stimuli converge. The intensity of the mitogen-activated protein kinase (MAPK) cascade activation influences the cellular response to Ras. Despite the fundamental role of p53 in Ras-induced growth arrest and senescence, it remains unclear how the Ras/MEK/ERK pathway induces growth arrest in the absence of p53. We report here that oncogenic Ras stabilizes p73 resulting in p73 accumulation and enhancement of its activity. p73, in turn, induces a sustained activation of the MAP kinase cascade synergizing with oncogenic Ras. We also found that inhibition of p73 function modifies the cellular outcome to Ras activation inhibiting Ras-dependent differentiation. Here, we show for the first time that there is a signaling loop between Ras-dependent MAPK cascade activation and p73 function.Cell Death and Differentiation advance online publication, 28 April 2006; doi:10.1038/sj.cdd.4401945.

PMID: 16645632 [PubMed - as supplied by publisher]