Phosphorylation of ASPP2 by RAS/MAPK Pathway Is Critical for Its Full Pro-Apoptotic Function

• DOI: 10.1371/journal.pone.0082022
• Publication Date: 2013-12-02T21:49:51Z
• Authors: Nadia Godin-Heymann; Yihua Wang; Elizabeth Slee; Xin Lu
• Keywords: 0301 basic medicine; MAP Kinase Signaling System; Science; Q; Molecular Sequence Data; R; Apoptosis; Protein Transport; 03 medical and health sciences; Cell Line, Tumor; ras Proteins; Medicine; Humans; Amino Acid Sequence; Mitogen-Activated Protein Kinases; Phosphorylation; Tumor Suppressor Protein p53; Apoptosis Regulatory Proteins; Research Article

We reported recently that apoptosis-stimulating protein of p53 (ASPP) 2, an activator p53, co-operates with oncogenic RAS to enhance the transcription and apoptotic function p53. However, detailed mechanism remains unknown. Here we show ASPP2 is a novel substrate mitogen-activated kinase (MAPK). Phosphorylation by MAPK required for RAS-induced increased binding transactivation pro-apoptotic genes. In contrast, phosphorylation mutant exhibits reduced fails apoptosis. Thus RAS/MAPK pathway provides link between in regulating