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

Cell Death and Differentiation
B Fernandez-GarciaMaria Carmen Marin

Abstract

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.

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Citations

Jul 6, 2013·Cell Death & Disease·L Gonzalez-CanoM C Marín
Jun 11, 2009·The Journal of Biological Chemistry·Fernando Marqués-GarcíaMaría C Marín
Nov 10, 2012·Investigative Ophthalmology & Visual Science·Siva S RadhakrishnanGregory S Schultz
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Mar 19, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Qizhi SunGregory M Kelly
Jul 17, 2015·Bioscience Reports·Dámaso Sánchez-CarreraCarlos Pipaón
Dec 7, 2018·Cell Death & Disease·Sandra Fuertes-AlvarezMaria C Marin
Apr 20, 2021·Nature Cancer·Suman MukhopadhyayFrank McCormick

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