Multiple sites of in vivo phosphorylation in the MDM2 oncoprotein cluster within two important functional domains

FEBS Letters

Hay, Trevor J¹  Meek, David W¹ 

[1] Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK

关键词: MDM2;    Phosphorylation;    p53;    Deletion analysis;   

DOI  :  10.1016/S0014-5793(00)01850-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The MDM2 oncoprotein is a negative regulatory partner of the p53 tumour suppressor. MDM2 mediates ubiquitination of p53 and targets the protein to the cytoplasm for 26S proteosome-dependent degradation. In this paper, we show that MDM2 is modified in cultured cells by multisite phosphorylation. Deletion analysis of MDM2 indicated that the sites of modification fall into two clusters which map respectively within the N-terminal region encompassing the p53 binding domain and nuclear export sequence, and the central acidic domain that mediates p14^ARF binding, p53 ubiquitination and cytoplasmic shuttling. The data are consistent with potential regulation of MDM2 function by multisite phosphorylation.

【 授权许可】

Unknown