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The MDM2 RING finger is required for cell cycle‐dependent regulation of its protein expression
Author(s) -
Gu Ling,
Ying Haoqiang,
Zheng Hongwu,
Murray Stephen A.,
Xiao Zhi-Xiong Jim
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00502-7
Subject(s) - ubiquitin ligase , ring finger , mdm2 , e2f1 , cell cycle , retinoblastoma protein , e2f , cell cycle protein , microbiology and biotechnology , ring finger domain , transcription factor , ubiquitin , f box protein , retinoblastoma , chemistry , transcription (linguistics) , biology , cell , cell culture , zinc finger , biochemistry , genetics , gene , linguistics , philosophy
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.