Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function

Journal article

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: Godin-Heymann, N; Wang, Y; Slee, E; Lu, X

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS ONE
• Volume: 8
• Issue: 12
• Pages: e82022
• Publication date: 2013-12-02
• Acceptance date: 2013-10-25
• DOI: 10.1371/journal.pone.0082022
• EISSN: 1932-6203
• Language: English
• Keywords: Humans; Tumor Suppressor Protein p53; Amino Acid Sequence; SBTMR; Mitogen-Activated Protein Kinases; ras Proteins; MAP Kinase Signaling System; Apoptosis Regulatory Proteins; Molecular Sequence Data; Apoptosis; Protein Transport; Cell Line, Tumor; Phosphorylation