The functional interactions between the p53 and MAPK signaling pathways.
The p53 tumor suppressor protein exerts its growth inhibitory activity by activating and interacting with diverse signaling pathways. As a downstream target, p53 protein is phosphorylated and activated by a number of protein kinases in response to stressful stimuli. As an upstream activator, activated p53 acts as a transcription factor to induce and/or suppress a number of genes whose expression leads to the activation of diverse signaling pathways. p53 protein can also interact with a number of proteins, resulting in an increase or decrease in p53 activity itself. The activation of p53 leads to many outcomes in cells, including cell cycle arrest and apoptosis. It has become clear that the p53 protein can functionally interact with the mitogen-activated protein kinase (MAPK) pathways, including the stress-activated protein kinase [SAPK/c-Jun N-terminal protein kinase (JNK)], the p38 mitogen-activated protein kinase (MAPK), and the extracellular signal related kinase (ERK). Upon exposure to stressful stimuli, MAP kinases phosphorylate and activate p53, leading to p53-mediated cellular responses. Recent studies have suggested a role of p53 as an upstream activator to regulate MAPK signaling via the transcriptional activation of members of the dual specificity phosphatase family. Because both the p53 and MAPK signaling pathways are altered in the majority of human tumors, understanding their functional interaction may provide new insights into the deregulated cell proliferation and survival that is characteristic of cancer.
Wu
Gen Sheng
GS
Program in Molecular Biology and Human Genetics, Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, Room E216, The Prentis Building, 110 East Warren Avenue, Detroit, Michigan 48201, USA. wug@karmanos.org
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016159:Tumor Suppressor Protein p53