Abstract
We reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an activator of p53, co-operates with oncogenic RAS to enhance the transcription and apoptotic function of p53. However, the detailed mechanism remains unknown. Here we show that ASPP2 is a novel substrate of mitogen-activated protein kinase (MAPK). Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes. In contrast, an ASPP2 phosphorylation mutant exhibits reduced p53 binding and fails to enhance transactivation and apoptosis. Thus phosphorylation of ASPP2 by RAS/MAPK pathway provides a novel link between RAS and p53 in regulating apoptosis.
MeSH terms
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Amino Acid Sequence
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Apoptosis Regulatory Proteins / chemistry
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Apoptosis Regulatory Proteins / metabolism*
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Apoptosis*
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Cell Line, Tumor
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Humans
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MAP Kinase Signaling System*
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Mitogen-Activated Protein Kinases / metabolism*
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Molecular Sequence Data
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Phosphorylation
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Protein Transport
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Tumor Suppressor Protein p53 / metabolism
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ras Proteins / metabolism*
Substances
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Apoptosis Regulatory Proteins
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TP53BP2 protein, human
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Tumor Suppressor Protein p53
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Mitogen-Activated Protein Kinases
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ras Proteins
Grants and funding
This work is supported by the Ludwig Institute for Cancer Research Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.