The MDM2 RING finger is required for cell cycle‐dependent regulation of its protein expression

FEBS Letters

Gu, Ling¹  Zheng, Hongwu¹  Xiao, Zhi-Xiong Jim¹  Ying, Haoqiang¹  Murray, Stephen A.¹ 

[1] Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, K423, Boston, MA 02118, USA

关键词: MDM2;    Cell cycle;    E3 ligase;    RING finger;    E2F;    Protein expression;    MDM2;    murine double minute-2;    RB;    retinoblastoma protein;   

DOI  :  10.1016/S0014-5793(03)00502-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The MDM2 oncoprotein is overexpressed in many human tumors and cancers. MDM2 functions as an E3 ligase for p53 and for itself. MDM2 also interacts with the retinoblastoma protein (RB) and the transcription factor E2F1 to promote cell cycle S-phase entry. Here, we report that MDM2 protein expression is cell cycle-regulated, which is dependent on its RING finger domain and requires Lys446. We show that MDM2 protein is stabilized at S phase. In addition, overexpression of MDM2 results in stimulation of E2F activity and accumulation of cells in S phase. These data suggest that ubiquitination of MDM2 is cell cycle-regulated and that MDM2 may play a role in cell cycle progression.

【 授权许可】

Unknown