TY - JOUR
T1 - A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein
AU - Milne, Diane
AU - Kampanis, Petros
AU - Nicol, Samantha
AU - Dias, Sylvia
AU - Campbell, David G.
AU - Fuller-Pace, Frances
AU - Meek, David
PY - 2004/11/5
Y1 - 2004/11/5
N2 - MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein. Phosphorylation of MDM2 by the protein kinase AKT is thought to regulate MDM2 function in response to survival signals, but there has been uncertainty concerning the identity of the sites phosphorylated by AKT. In the present study, we identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro. Analysis of MDM2 in cultured cells confirms that Ser-166 and Ser-188 are phosphorylated by AKT in a physiological context.
AB - MDM2 is an E3 ubiquitin ligase which mediates ubiquitylation and proteasome-dependent degradation of the p53 tumor suppressor protein. Phosphorylation of MDM2 by the protein kinase AKT is thought to regulate MDM2 function in response to survival signals, but there has been uncertainty concerning the identity of the sites phosphorylated by AKT. In the present study, we identify Ser-166, a site previously reported as an AKT target, and Ser-188, a novel site which is the major site of phosphorylation of MDM2 by AKT in vitro. Analysis of MDM2 in cultured cells confirms that Ser-166 and Ser-188 are phosphorylated by AKT in a physiological context.
U2 - 10.1016/j.febslet.2004.09.081
DO - 10.1016/j.febslet.2004.09.081
M3 - Article
C2 - 15527798
SN - 0014-5793
VL - 577
SP - 270
EP - 276
JO - FEBS Letters
JF - FEBS Letters
IS - 1-2
ER -