title: Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function.
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.
authors: Ludwig Institute for Cancer Research Ltd., Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors: Nadia
authors: N
authors: Godin-Heymann
authors: Yihua
authors: Y
authors: Wang
authors: Elizabeth
authors: E
authors: Slee
authors: Xin
authors: X
authors: Lu
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D021381:Protein Transport; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins