HDM2 phosphorylation by MAPKAP kinase 2
Open Access
- 31 January 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 24 (12), 1965-1972
- https://doi.org/10.1038/sj.onc.1208389
Abstract
P53 stability is regulated by HDM2, a RING domain protein that acts as an E3 ligase to ubiquitinate p53 and target its degradation. Phosphorylation of HDM2 on serine 166 by AKT has been shown to enhance HDM2 activity and promote the degradation of p53. Here, we show that MAPKAP kinase 2 (MK2) can phosphorylate HDM2 on serine 157 and 166 in vitro. Treatment of cells with anisomycin, which activates MK2, also results in phosphorylation of HDM2 on serine 157 and 166 in vivo. Mutation of the MK2 phosphorylation sites in HDM2 to aspartic acid renders HDM2 slightly more active in the degradation of p53, and mouse cells deficient for MK2 show reduced Mdm2 phosphorylation and elevated levels of p53 protein. Together, our results suggest that MK2 may act to dampen the extent and duration of the p53 response.This publication has 45 references indexed in Scilit:
- The ubiquitin ligase COP1 is a critical negative regulator of p53Nature, 2004
- Phage-peptide Display Identifies the Interferon-responsive, Death-activated Protein Kinase Family as a Novel Modifier of MDM2 and p21WAF1Journal of Molecular Biology, 2004
- Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 DegradationCell, 2003
- mdm2 Is Critical for Inhibition of p53 during Lymphopoiesis and the Response to Ionizing IrradiationMolecular and Cellular Biology, 2003
- Hypophosphorylation of Mdm2 Augments p53 StabilityMolecular and Cellular Biology, 2002
- Identification of p53 Sequence Elements That Are Required for MDM2-Mediated Nuclear ExportMolecular and Cellular Biology, 2001
- C-Terminal Ubiquitination of p53 Contributes to Nuclear ExportMolecular and Cellular Biology, 2001
- Regulation of p53 stability by Mdm2Nature, 1997
- Mdm2 promotes the rapid degradation of p53Nature, 1997
- p38/RK is essential for stress-induced nuclear responses: JNK/SAPKs and c-Jun/ATF-2 phosphorylation are insufficientCurrent Biology, 1996